Updated on 2025/04/09

写真a

 
Yamamoto Kazuhiro
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
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Degree

  • 博士(薬学) ( 京都薬科大学大学院薬学研究科 )

Research Interests

  • Interstitial lung disease

  • 皮膚障害

  • Chronic kidney disease

  • OncoNephrology

  • target therapy drugs

Research Areas

  • Life Science / Pharmacology  / 臨床薬理学

  • Life Science / Clinical pharmacy

  • Life Science / Molecular biology

  • Life Science / Pharmacology  / 薬物動態学

Education

  • Kyoto Pharmaceutical University   薬学研究科   臨床薬学専攻修士課程

    2007.4 - 2009.3

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  • Kyoto Pharmaceutical University   薬学部  

    2003.4 - 2007.3

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Research History

  • 岡山大学 学術研究院医歯薬学域   教授

    2024.5

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    Country:Japan

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  • Kobe University

    2024.5

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  • 神戸大学医学部附属病院   講師・副薬剤部長

    2022.4 - 2024.4

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  • 神戸大学医学部附属病院   講師

    2020.3 - 2022.3

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  • Kobe University   University Hospital

    2018.9 - 2020.2

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  • Kobe University   University Hospital

    2017.7 - 2018.8

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  • Kobe Pharmaceutical University

    2015

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  • Okayama University   Faculty of Pharmaceutical Sciences

    2015 - 2016

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  • Kobe University   University Hospital

    2009.4

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Professional Memberships

  • 日本臨床化学会

    2023.6

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  • 日本臨床薬理学会

    2019

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  • International Association of Therapeutic Drug Monitoring and Clinical Toxicology

    2017.4

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  • 日本TDM学会

    2012.6

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  • 日本腎臓病薬物療法学会

    2011.4

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  • JAPANESE SOCIETY OF PHARMACEUTICAL HEALTH CARE AND SCIENCES

    2007.6

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  • THE PHARMACEUTICAL SOCIETY OF JAPAN

    2007.2

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Committee Memberships

  • 日本臨床薬理学会   社員  

    2023.12   

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    Committee type:Academic society

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  • 日本臨床化学会   TDM専門委員会  

    2023.6   

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  • 関西腎と薬剤研究会   副会長  

    2021.1 - 2024.12   

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  • 日本腎臓病薬物療法学会   統計調査委員会  

    2020.11   

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  • 日本腎臓病薬物療法学会   学術委員会  

    2020.11   

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  • 日本腎臓病薬物療法学会   代議員  

    2020.11   

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  • 日本腎臓病薬物療法学会   がん薬物療法時の腎障害診療ガイドライン改訂委員会  

    2020.10 - 2022.10   

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  • 日本医療薬学会   編集委員会  

    2020.4   

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  • 日本医療薬学会   代議員  

    2019.3   

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  • 日本医療薬学会   薬物療法専門薬剤師・認定薬剤師認定試験問題作成小委員会  

    2018.4 - 2024.3   

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  • 日本医療薬学会   薬物療法専門薬剤師・認定薬剤師認定試験実行小委員会  

    2018.4 - 2024.3   

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  • 日本腎臓病薬物療法学会   学会誌編集委員会  

    2016.11   

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Papers

  • Prolonged Prothrombin Time due to Drug-Drug Interaction of Warfarin after the Change from Bosentan to Macitentan: A Case of Pharmacist Intervention in the Outpatient Clinic.

    Tomoko Kurimura, Tomohiro Omura, Kazuhiro Yamamoto, Hidekazu Tanaka, Takeshi Kimura, Kotaro Itohara, Yumi Kitahiro, Yasushi Habu, Toshiyasu Sakane, Ikuko Yano

    The Kobe journal of medical sciences   70 ( 4 )   E125-E129   2025.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    A woman in her 70s who was taking warfarin 3.75 mg/day had a prothrombin time-international normalized ratio (PT-INR) within the therapeutic range. Her medication for pulmonary hypertension was changed from bosentan to macitentan. After 40 days, she developed respiratory distress, anorexia, and vomiting caused by common cold. When she visited the pharmaceutical outpatient clinic without reservation, the pharmacist suspected that bosentan discontinuation, which cancelled cytochrome P450 (CYP) 2C9 and CYP3A4 enzyme induction, and decreased vitamin K intake due to appetite loss had enhanced warfarin effect, causing PT-INR prolongation. The pharmacist requested the physician to examine the patient's PT-INR. Results showed that her PT-INR was >7. Hence, she was urgently hospitalized. Warfarin and macitentan were discontinued, and the patient's PT-INR decreased to 1.77 after the intravenous administration of vitamin K. Her appetite improved, and warfarin 2 mg/day was resumed. Additionally, when she had been administered macitentan, her hemoglobin levels decreased from 10.8 to 6.6 mg/dL. Therefore, the pharmacist and the physician during hospitalization planned to resume treatment with bosentan, but not with macitentan. The pharmacist proposed to increase the warfarin dose to 3.75 mg since the bosentan and warfarin interaction could lower PT-INR. Thereafter, the patient's PT-INR was controlled within the therapeutic range, and her hemoglobin level was 8-9 mg/dL. The patient was discharged on day 17 of admission. Thus, pharmacist intervention plays a significant role in warfarin control with consideration of drug-drug interaction in patients receiving pulmonary hypertension treatment.

    DOI: 10.24546/0100492951

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  • Involvement of everolimus‑induced ABCB1 downregulation in drug‑drug interactions. Reviewed International journal

    Yuko Nakayama, Aya Ino, Kazuhiro Yamamoto, Kohji Takara

    Biomedical reports   21 ( 6 )   184 - 184   2024.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    Everolimus is an oral mammalian target of rapamycin (mTOR) inhibitor used in cancer chemotherapy and transplantation. Due to its therapeutic properties, everolimus has been used long-term in clinical practice. Drug interactions with everolimus during gastrointestinal absorption can alter the oral bioavailability of everolimus and/or concomitant drugs. However, the effects of everolimus on gastrointestinal absorption remain unknown. The present study assessed the impact of continuous exposure to everolimus on expression and function of the ATP-binding cassette (ABC) transporter ABCB1 and ABCG2 using a Caco-2 intestinal cell model. Caco-2 subline, Caco/EV, was established by continuously exposing Caco-2 cells to 1 µM everolimus. Cell viability was evaluated using WST-1 assay. mRNA levels were measured by reverse transcription-quantitative PCR. Transport activity of ABCB1 was evaluated through the cellular accumulation of Rhodamin 123, a substrate for ABCB1. The half-maximal inhibitory concentration (IC50) values for everolimus in Caco-2 and Caco/EV cells were 0.31 and 4.33 µM, respectively, indicating 14-fold resistance in Caco/EV cells. Sensitivity to paclitaxel and 7-ethyl-10-hydroxycamptothecin, which are substrates for ABCB1 and ABCG2, respectively, was enhanced in Caco/EV, but not in Caco-2 cells. The IC50 values of cisplatin were comparable in both cell lines. Furthermore, mRNA expression levels of ABCB1 and ABCG2 were lower in Caco/EV cells than in Caco-2 cells, and the cellular accumulation of Rhodamine 123 was significantly higher in Caco/EV cells. These findings demonstrated that continuous exposure to everolimus suppressed the expression and function of ABCB1 and ABCG2, suggesting potential drug-drug interactions via the suppression of ABCB1 and ABCG2 in the intestinal tract.

    DOI: 10.3892/br.2024.1872

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  • Pharmacokinetic and Pharmacodynamic Assessment of Valganciclovir in Infants With Congenital Cytomegalovirus Infection. Reviewed International journal

    Kotaro Itohara, Kazuhiro Yamamoto, Shunsuke Fujinaka, Mari Hashimoto, Naoki Tamura, Yumi Kitahiro, Tomohiro Omura, Kazumichi Fujioka, Ikuko Yano

    Therapeutic drug monitoring   2024.9

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    BACKGROUND: Valganciclovir (VGCV) is administered at a dose of 16 mg/kg 2 times daily for 6 months to treat symptomatic congenital cytomegalovirus (CMV) infections. During the treatment period, approximately 20% of the patients developed grade 3 or higher neutropenia. Currently, information on the pharmacokinetics and pharmacodynamics of ganciclovir, an active metabolite of VGCV, in infants is limited. In the current study, the relationship between ganciclovir concentration and neutropenia was investigated, and a population pharmacokinetic (PPK) model of ganciclovir in infants with symptomatic congenital CMV infection was developed. METHODS: Japanese infants who were prescribed oral VGCV for symptomatic congenital CMV infections between July 2017 and January 2021 were included. The relationship between the observed trough ganciclovir concentrations and neutrophil counts was examined. PPK analysis was performed to evaluate the covariates affecting the pharmacokinetics of ganciclovir. RESULTS: Twenty-seven ganciclovir serum samples from 8 patients were analyzed. A moderate negative correlation was observed between the observed trough ganciclovir concentration and neutrophil count. PPK model analysis showed that postmenstrual age (PMA) affected the total body clearance of ganciclovir after correcting for the empirical allometric scaling of body weight. Based on PMA and body weight, a nomogram to achieve the target area under the concentration-time curve from 0 to 24 hours of 40-60 mcg·h·mL-1 of ganciclovir was calculated. CONCLUSIONS: The relationship between neutrophil count and ganciclovir trough concentration in infants was clarified. The PPK model showed that the dose of VGCV should be reduced in patients with a low PMA to achieve target exposure.

    DOI: 10.1097/FTD.0000000000001257

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  • Evaluation of the drug-drug interactions management system for appropriate use of nirmatrelvir/ritonavir: a retrospective observational study. Reviewed International journal

    Takeshi Tomida, Takeshi Kimura, Kazuhiro Yamamoto, Atsushi Uda, Yuki Matsumoto, Naoki Tamura, Masashi Iida, Akiko Tanifuji, Kumiko Matsumoto, Naomi Mizuta, Kei Ebisawa, Goh Ohji, Tomohiro Omura, Kentaro Iwata, Ikuko Yano

    Journal of pharmaceutical health care and sciences   10 ( 1 )   54 - 54   2024.9

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    PURPOSE: While nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r. METHODS: A retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality. RESULTS: This study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1-3.1]. CONCLUSIONS: Most patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.

    DOI: 10.1186/s40780-024-00376-4

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  • オピオイド鎮痛薬を入院中に開始した外来頭頸部がん患者を対象とした病院薬剤師による電話サポート介入の効果 Reviewed

    志田 有里, 飯田 真之, 番匠 咲帆, 蓼原 瞬, 大本 暢子, 山本 和宏, 大村 友博, 丹生 健一, 矢野 育子

    日本緩和医療薬学雑誌   17 ( 3 )   87 - 94   2024.9

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    Language:Japanese   Publisher:(一社)日本緩和医療薬学会  

    入院中にオピオイド鎮痛薬(オピオイド)を導入し外来移行した頭頸部がん患者に対し,病院薬剤師が電話で定期的に疼痛評価やオピオイド副作用評価を行い(電話サポート),必要時に薬剤調整などを医師に提案する取組みを行い,その効果を評価したので報告する.解析対象患者は10名,電話サポートの期間と回数の中央値はそれぞれ123日と5回であり,患者から薬剤師への相談は40件,薬剤師から医師への提案は53件であった.疼痛強度を示す1日平均numerical rating scaleは介入前後で5.5から1.0と有意に低下し,エドモントン症状評価システム改訂版による副作用評価では倦怠感と便秘の項目で介入前後の変化量がそれぞれ-2.5,-4.5と有意に低下した.以上,外来頭頸部がん患者への薬剤師による電話サポートはオピオイドによる疼痛緩和や副作用回避に有用であり,オピオイド適正使用に繋がることが示唆された.(著者抄録)

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  • Calvert式に用いる腎機能指標とカルボプラチンによる血液毒性発現の関連

    小林 理乃, 山本 和宏, 丹田 雅明, 糸原 光太郎, 北廣 優実, 大村 友博, 矢野 育子

    TDM研究   41 ( 2 )   158 - 158   2024.7

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    Language:Japanese   Publisher:(一社)日本TDM学会  

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  • Down-regulation of ABCB1 in Everolimus-resistant Renal Cell Carcinoma Cells. Reviewed International journal

    Yuko Nakayama, Aya Ino, Kazuhiro Yamamoto, Kohji Takara

    Anticancer research   44 ( 7 )   2871 - 2876   2024.7

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    BACKGROUND/AIM: Everolimus-resistant Caki/EV and 786/EV cells have been established from human derived renal cell carcinoma cells, Caki-2 and 786-O, respectively. These cells exhibit resistance to everolimus and to other mTOR inhibitors and erlotinib. However, the sensitivity of these resistant cells to classical and cytotoxic anticancer drugs remain unclear. The aim of the study was to examine sensitivity of Caki/EV and 786/EV cells to classical and cytotoxic anticancer drugs. MATERIALS AND METHODS: Sensitivity to classical and cytotoxic anticancer drugs in Caki/EV and 786/EV cells was evaluated using the WST-1 (tetrazolium salts) colorimetric assay and was compared to those of the corresponding parental cells. The mRNA expression levels were measured using SYBR® green based quantitative reverse transcription-polymerase chain reaction. RESULTS: Sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin, etoposide, SN-38 (active metabolite of irinotecan), 5-fluorouracil, cisplatin, and carboplatin varied in the resistant cells. Sensitivity to carboplatin and SN-38 was comparable between resistant cells and their parental cells, whereas sensitivity to vinca alkaloids, etoposide, 5-fluorouracil, and cisplatin decreased in the resistant cells. However, sensitivity to paclitaxel and doxorubicin was remarkably enhanced in both resistant cells compared to that of parental cells, this could be partially explained by down-regulation of ABCB1 mRNA expression. CONCLUSION: The everolimus-resistant Caki/EV and 786/EV cells showed cross-resistance to classical and cytotoxic anticancer drugs. However, Caki/EV and 786/EV cells exhibited a remarkable increase in sensitivity to paclitaxel and doxorubicin, and ABCB1 mRNA was down-regulated in response to long-term exposure to everolimus.

    DOI: 10.21873/anticanres.17099

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  • Cystine and theanine for chemoradiotherapy-induced esophagitis in non-small cell lung cancer: a prospective observational study. Reviewed International journal

    Misato Kariya, Kazuhiro Yamamoto, Akira Kawamura, Shiho Tanizaki, Keiko Ueda, Kastuko Sai, Akito Hata

    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer   32 ( 6 )   400 - 400   2024.6

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    PURPOSE: Although several potential radioprotectants have been explored, radiation esophagitis is still difficult to control. Further development of supportive therapies is required. Our purpose was to investigate the efficacy and safety of cystine and theanine for esophagitis in non-small cell lung cancer (NSCLC) patients undergoing chemoradiotherapy (CRT). METHODS: This study is a prospective observational study. The participants were recruited from unresectable locally advanced NSCLC who had scheduled to receive weekly paclitaxel or nab-paclitaxel/carboplatin plus radiation therapy (60 Gy in 30 fractions) for 6 weeks. They took an oral amino acid supplement containing 700 mg cystine and 280 mg theanine once daily regardless of CRT timing from the start of CRT until completion. The primary endpoint was the incidence of any grade esophagitis. The secondary endpoints were quality of life (QoL) and adverse events (AEs). RESULTS: A total of 26 patients were evaluated. All participants completed 60 Gy of RT in 30 fractions. The overall incidence of esophagitis was 73%; however, no ≥ grade 3 was reported. There were no AEs likely to be related to cystine and theanine. The mean EuroQoL 5-Dimension 5-Level health index score before and after chemoradiotherapy was 0.952 ± 0.0591 and 0.952 ± 0.0515 (P = 0.89), and the mean Visual Analogue Scale scores before and after treatment were 67.9 ± 15.4 and 79.4 ± 13.2 (P = 0.0047), respectively. CONCLUSION: Our study showed no severe esophagitis, any AEs, nor QoL decrease in NSCLC patients receiving CRT. Cystine and theanine are potentially effective to reduce severe CRT-induced esophagitis. TRIAL REGISTRATION: UMIN000052622, 26 October 2023, retrospectively registered.

    DOI: 10.1007/s00520-024-08613-0

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  • 院外処方における臨床検査値を用いた2段階チェック機能の有用性 処方禁忌警告システムと処方箋への検査値印字 Reviewed

    冨田 猛, 山本 和宏, 木村 丈司, 宇田 篤史, 土生 康司, 大本 暢子, 山下 和彦, 大村 友博, 矢野 育子

    医療薬学   50 ( 6 )   277 - 286   2024.6

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    Language:Japanese   Publisher:(一社)日本医療薬学会  

    院外処方における処方禁忌チェックシステムと院外処方箋における検査値印字による2段階チェックの有用性について評価した。処方禁忌チェックは2018年8月から稼働し、その17ヵ月後の2020年1月から院外処方箋への検査値印字を開始したことを踏まえ、17ヵ月間を1期間として対象期間を設定した。各調査期間における禁忌アラート該当件数は第1期が9850件(3.62%)、第2期が9464件(3.29%)、第3期が9460件(3.41%)、第4期が9823件(3.34%)であり、第1期に比べて第2、3、4期の割合はいずれも有意に低下した。検査値関連の疑義照会による処方変更件数は第2期が5件、第3期が66件、第4期が47件であり、第2期に比べて第3期と第4期で検査値関連の疑義照会による処方変更件数は約10倍に増えており、割合としても有意に増加した。院外処方箋に検査値印字を行う2段階チェックは医薬品の適正使用の推進に有用であることが示された。

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  • Population pharmacokinetics of everolimus in renal transplant recipients receiving long-term multiple immunosuppressive therapy. Reviewed International journal

    Tomoyuki Sakaue, Kazuhiro Yamamoto, Kotaro Itohara, Yumi Kitahiro, Takahito Endo, Naoki Yokoyama, Takeshi Ishimura, Tomohiro Omura, Ikuko Yano

    Drug metabolism and pharmacokinetics   56   101009 - 101009   2024.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    Everolimus is used for immunosuppression after renal transplantation. This study aimed to develop a population pharmacokinetic (PopPK) model of everolimus using therapeutic drug monitoring (TDM) data of patients under long-term multiple immunosuppressive therapy, including tacrolimus. To develop the model, 185 renal transplant recipients with 3358 everolimus blood concentrations during a median postoperative period of 35.3 months were included. The PopPK model is described as a one-compartment model with first-order absorption. The population mean of apparent clearance is 8.92 L/h (relative standard error = 3.6%), and this negatively correlated with the dose-normalized concentration (C/D) of tacrolimus and hematocrit value, and positively correlated with a daily dose of everolimus (i.e. TDM effect). The usefulness of dose adjustment using the final popPK model was assessed by a simulation study. The ratio of the first trough measurement within the therapeutic range of 3-8 ng/mL increased from 69.8% in the original dose to 87.9% in the individual dose calculated by the final PopPK model. The tacrolimus C/D ratio before initiating everolimus therapy and the hematocrit value were useful to estimate the initial dose of everolimus and can improve the safety and effectiveness of immunosuppressive therapy involving everolimus.

    DOI: 10.1016/j.dmpk.2024.101009

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  • Effect of early dose reduction of osimertinib on efficacy in the first-line treatment for EGFR-mutated non-small cell lung cancer. International journal

    Tomoki Hori, Kazuhiro Yamamoto, Takefumi Ito, Shigeki Ikushima, Tomohiro Omura, Ikuko Yano

    Investigational new drugs   42 ( 3 )   281 - 288   2024.6

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Osimertinib is used as the first-line therapy for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, early dose reduction is often required due to adverse events (AEs). This study aimed to evaluate the effect of early dose reduction of osimertinib on efficacy and safety. This was a retrospective study including patients with EGFR-mutated NSCLC who were started on osimertinib as the first-line therapy between August 2018 and December 2021. Patients whose doses were reduced to less than 80 mg/day within 6 months of osimertinib initiation or started at 40 mg/day were defined as the dose reduction group. The primary endpoint was progression-free survival (PFS). Factors affecting PFS were explored using the Cox proportional hazards model. A total of 85 patients were included in this study. No significant differences in patient characteristics were observed between the dose reduction (n = 25) and standard dose groups (n = 60). The median PFS in the dose reduction group was significantly prolonged compared with that in the standard dose group (26.0 months vs. 12.0 months, p = 0.03). Multivariable analysis of 84 patients, excluding a patient with unknown brain metastasis, revealed that EGFR exon 21 L858R mutation, malignant pleural effusion or pleural metastasis, liver metastasis, and dose reduction within 6 months were independent factors affecting PFS. Early dose reduction of osimertinib is an effective therapeutic strategy for prolonging PFS in patients with EGFR-mutated NSCLC.

    DOI: 10.1007/s10637-024-01432-4

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  • Pharmacokinetics of Brexpiprazole, Quetiapine, Risperidone, and Its Active Metabolite Paliperidone in a Postpartum Woman and Her Baby. Reviewed International journal

    Toru Konishi, Yumi Kitahiro, Naoko Fujiwara, Kazuhiro Yamamoto, Mari Hashimoto, Takahiro Ito, Kotaro Itohara, Kazumichi Fujioka, Hitomi Imafuku, Ikuo Otsuka, Tomohiro Omura, Ikuko Yano

    Therapeutic drug monitoring   46 ( 5 )   687 - 691   2024.4

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    BACKGROUND: Brexpiprazole is a second-generation antipsychotic approved in Japan in 2018; however, information on placental passage and breast milk transfer remains limited. In this report, the patient, a 30-year-old pregnant woman with schizophrenia, was medicated with brexpiprazole, risperidone, and quetiapine. METHODS: The study used high-performance liquid chromatography-tandem mass spectrometry to determine the concentrations of brexpiprazole, quetiapine, risperidone, and its active metabolite (paliperidone) in maternal and neonatal plasma, cord venous plasma, and breast milk. Maternal plasma samples were obtained approximately 2 and 8 hours after the last administration of antipsychotics on the day of delivery and at the estimated drugs' trough time on days 1, 3, and 5 after delivery. RESULTS: The maternal plasma concentrations of brexpiprazole, quetiapine, and paliperidone increased by approximately 3.5-fold on the fifth day compared with those on the day of delivery, whereas the risperidone concentration remained almost constant. Moreover, the neonatal plasma concentrations of the 4 drugs immediately after birth were indistinguishable from the umbilical cord concentrations and gradually decreased, except for risperidone. Relative infant doses of these compounds were below 1.1%. CONCLUSIONS: Pregnancy status notably alters the pharmacokinetic properties of antipsychotics. Therefore, close and careful monitoring of clinical symptoms should be considered during pregnancy and after delivery. Although brexpiprazole is transferred to neonates through the placenta, breastfeeding is still possible because the relative infant dose value of this drug was much less than 10%.

    DOI: 10.1097/FTD.0000000000001197

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  • テルミサルタン錠の変色原因は添加剤のメグルミンによるドパミン誘導体の分解物である Reviewed

    岡崎 裕太朗, 大村 友博, 上田 昌史, 武田 紀彦, 竹下 治範, 飯田 真之, 山下 和彦, 木村 丈司, 大本 暢子, 山本 和宏, 土生 康司, 宮田 興子, 矢野 育子

    日本病院薬剤師会雑誌   60 ( 4 )   395 - 401   2024.4

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    一包化錠剤仕分け装置の運用過程でテルミサルタン錠の変色を経験した。まず,テルミサルタン錠とドパミン誘導体を含む錠剤(レボドパ/カルビドパ錠,ドロキシドパ錠または粉砕したメチルドパ錠)との接触実験を行ったところ着色を確認した。一方で,テルミサルタンとドパミン誘導体が構造的に化学反応する可能性は低いため,テルミサルタン錠の添加剤であるメグルミンに着目し,メチルドパと混合下で基礎的検討を行った。水分存在下では着色が加速し,着色成分の質量分析を行った結果,複数のメチルドパ分解産物の生成が示された。すなわちドパミン誘導体は水分存在下でメグルミンと接触することで酸化的に分解され,さらに重合することでメラニン類似物質となり,それがテルミサルタン錠の変色原因であることが示唆された。以上,添加剤としてメグルミンを含有する薬剤では,無包装下でドパミン誘導体との接触による製剤学的相互作用に注意を要する。(著者抄録)

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J04451&link_issn=&doc_id=20240411310006&doc_link_id=%2Fdg4hppha%2F2024%2F006004%2F006%2F0395-0401%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg4hppha%2F2024%2F006004%2F006%2F0395-0401%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • The Efficacy of Bepotastine Besilate Compared With Hydroxyzine Pamoate for Preventing Infusion Reactions to the First Dose of Rituximab in Patients With Non-Hodgkin Lymphoma: Protocol for a Phase II, Double-Blind, Multicenter Randomized Trial. Reviewed International journal

    Yumi Kitahiro, Kazuhiro Yamamoto, Kimikazu Yakushijin, Takeshi Ioroi, Masaaki Tanda, Kotaro Itohara, Tomohiro Omura, Hironobu Minami, Ikuko Yano

    JMIR research protocols   13   e54882   2024.2

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    BACKGROUND: Rituximab, an anti-CD20 monoclonal antibody, can cause infusion reactions (IRs), especially during the initial rituximab infusion therapy. Generally, patients are administered a histamine H1-receptor antagonist before the rituximab infusion, along with an antipyretic analgesic, to prevent or reduce IRs. Multiple retrospective case-control studies indicate that the second generation of histamine H1-receptor antagonists might be more effective than the first generation in suppressing IRs caused by the rituximab infusion. OBJECTIVE: This study aimed to assess the efficacy of first- and second-generation histamine H1-receptor antagonists for preventing IRs resulting from the initial infusion of rituximab in patients diagnosed with non-Hodgkin lymphoma. METHODS: This is a phase II, double-blind, active-controlled randomized trial. It will be a multicenter study conducted across 3 facilities that aims to enroll a total of 40 patients diagnosed with non-Hodgkin lymphoma who will receive their initial rituximab infusion. Participating patients will be administered hydroxyzine pamoate or bepotastine besilate, representing first- or second-generation histamine H1-receptor antagonists, respectively. This will be combined with 400-mg acetaminophen tablets taken approximately 30 minutes before the first infusion of rituximab. The primary end point of this trial is to assess severe IRs, equivalent to grade 2 or higher as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, that occur within a 4-hour period after the initiation of rituximab infusion. The secondary end points include assessing the severity of the initial IR, the maximum severity of the IR, and the duration between rituximab infusion initiation and the onset of the first IR within a 4-hour period. Additionally, the trial will evaluate histamine H1-receptor antagonist-induced drowsiness using the visual analogue scale, with each patient providing their individual response. RESULTS: This study began with patient recruitment in April 2023, with 17 participants enrolled as of November 12, 2023. The anticipated study completion is set for February 2026. CONCLUSIONS: This study is the first randomized controlled trial comparing the effects of oral first- and second-generation histamine H1-receptor antagonists in preventing IRs induced by the initial administration of rituximab. The findings from this study hold the potential to establish the rationale for a phase III study aimed at determining the standard premedication protocol for rituximab infusion. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs051220169; https://jrct.niph.go.jp/latest-detail/jRCTs051220169. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54882.

    DOI: 10.2196/54882

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  • 潜在的不適切処方の中止維持における退院時薬剤情報提供の効果 Reviewed

    古江 由依, 山本 和宏, 木村 丈司, 高橋 知子, 川瀬 愛子, 清水 倫子, 飯田 真之, 松本 久美子, 大本 暢子, 山下 和彦, 大村 友博, 坂根 稔康, 國正 淳一, 矢野 育子

    医療薬学   50 ( 2 )   75 - 83   2024.2

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    退院時薬剤情報提供が入院中に中止した潜在的不適切処方(PIMs)の中止維持に有用であるかについて検討するため、入院中にPIMsを中止して退院した65歳以上の循環器内科・心臓血管外科病棟患者について後方視的調査を行った。その結果、お薬手帳を用いた退院時薬剤情報提供を実施した群におけるPIMsの中止維持薬剤割合は86.1%と高く、薬剤情報提供が個別のPIMsの中止維持に有効であることが示唆された。PIMsの再開と関連する因子として中止維持の評価時点が再入院時であることが特定され、お薬手帳を介して退院時薬剤情報が共有されないまま他院へ通院することがPIMs再開のリスクとなることが示唆された。退院時の薬剤情報提供は、診療情報が共有されない他院への通院患者において一般的に回避すべきPIMsの中止維持に有効であり、より安全で一貫性のある薬物治療の提供に貢献できると考えられた。

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  • Correction to: Clinical questions and good practice statements of clinical practice guidelines for management of kidney injury during anticancer drug therapy 2022.

    Motoko Yanagita, Satoru Muto, Hiroyuki Nishiyama, Yuichi Ando, Sumio Hirata, Kent Doi, Yutaka Fujiwara, Norio Hanafusa, Takahiro Hatta, Junichi Hoshino, Satoko Ichioka, Takamitsu Inoue, Kenji Ishikura, Taigo Kato, Hiroshi Kitamura, Yusuke Kobayashi, Yuichi Koizumi, Chihiro Kondoh, Takeshi Matsubara, Kazuo Matsubara, Koji Matsumoto, Yusuke Okuda, Yuta Okumura, Emiko Sakaida, Yugo Shibagaki, Hideki Shimodaira, Nao Takano, Akiko Uchida, Kimikazu Yakushijin, Takehito Yamamoto, Kazuhiro Yamamoto, Yoshinari Yasuda, Mototsugu Oya, Hirokazu Okada, Masaomi Nangaku, Naoki Kashihara

    Clinical and experimental nephrology   28 ( 2 )   123 - 124   2024.2

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  • 分子標的型抗がん薬による間質性肺疾患発症の分子機構に基づく予測法の開発 mTOR阻害薬による間質性肺疾患とSTAT3の関連 Reviewed

    山本 和宏

    薬学雑誌   143 ( 11 )   911 - 916   2023.11

  • Clinical questions and good practice statements of clinical practice guidelines for management of kidney injury during anticancer drug therapy 2022. Reviewed

    Motoko Yanagita, Satoru Muto, Hiroyuki Nishiyama, Yuichi Ando, Sumio Hirata, Kent Doi, Yutaka Fujiwara, Norio Hanafusa, Takahiro Hatta, Junichi Hoshino, Satoko Ichioka, Takamitsu Inoue, Kenji Ishikura, Taigo Kato, Hiroshi Kitamura, Yusuke Kobayashi, Yuichi Koizumi, Chihiro Kondoh, Takeshi Matsubara, Kazuo Matsubara, Koji Matsumoto, Yusuke Okuda, Yuta Okumura, Emiko Sakaida, Yugo Shibagaki, Hideki Shimodaira, Nao Takano, Akiko Uchida, Kimikazu Yakushijin, Takehito Yamamoto, Kazuhiro Yamamoto, Yoshinari Yasuda, Mototsugu Oya, Hirokazu Okada, Masaomi Nangaku, Naoki Kashihara

    Clinical and experimental nephrology   2023.10

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    DOI: 10.1007/s10157-023-02415-0

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  • Molecular Characteristics of Everolimus-resistant Renal Cell Carcinoma Cells Generated by Continuous Exposure to Everolimus. Reviewed International journal

    Yuko Nakayama, Daichi Enomoto, Kazuhiro Yamamoto, Kohji Takara

    Anticancer research   43 ( 10 )   4349 - 4357   2023.10

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    BACKGROUND/AIM: Mammalian target of rapamycin (mTOR) inhibitors represent the standard of care for metastatic renal cell carcinoma (RCC). However, treatment outcomes are relatively poor, suggesting a potential problem with tolerating mTOR inhibitors. The aim of this study was to establish everolimus-resistant sublines and to compare their molecular characteristics with those of their counterparts. MATERIALS AND METHODS: Human-derived RCC, Caki-2, and 786-O cells were continuously exposed to everolimus at 1 μM, and the established resistant sublines were designated as Caki/EV and 786/EV, respectively. Cellular characteristics were compared between both cells. RESULTS: Caki/EV and 786/EV cells showed a decrease in sensitivity to everolimus as well as other mTOR inhibitors. Expression of mTOR and its effectors exhibited no alteration in resistant sublines and their counterparts. However, phosphorylation of S6K, an index of mTOR activity, decreased in resistant sublines. PCR array analysis of mTOR signaling pathway-related factors indicated that the expression of INSR, TP53, and IGFBP3 increased in Caki/EV cells, whereas that of TELO2, HRAS, and SGK1 was up-regulated in 786/EV cells. The levels of DDIT4, DEPTOR, HIF1A, and PLD1 mRNAs decreased in both cell lines. CONCLUSION: The novel everolimus-resistant Caki/EV and 786/EV cells exhibited cross-resistance to other mTOR inhibitors and decreased mTOR activity. Furthermore, down-regulation of DDIT4, DEPTOR, HIF1A, and PLD1 may contribute to everolimus resistance.

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  • Chapter 1: Evaluation of kidney function in patients undergoing anticancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022. Reviewed

    Satoru Muto, Takeshi Matsubara, Takamitsu Inoue, Hiroshi Kitamura, Kazuhiro Yamamoto, Taisuke Ishii, Masahiko Yazawa, Ryohei Yamamoto, Naoto Okada, Kiyoshi Mori, Hiroyuki Yamada, Takashige Kuwabara, Atsushi Yonezawa, Takuya Fujimaru, Haruna Kawano, Hideki Yokoi, Kent Doi, Junichi Hoshino, Motoko Yanagita

    International journal of clinical oncology   28 ( 10 )   1259 - 1297   2023.10

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    The prevalence of CKD may be higher in patients with cancer than in those without due to the addition of cancer-specific risk factors to those already present for CKD. In this review, we describe the evaluation of kidney function in patients undergoing anticancer drug therapy. When anticancer drug therapy is administered, kidney function is evaluated to (1) set the dose of renally excretable drugs, (2) detect kidney disease associated with the cancer and its treatment, and (3) obtain baseline values for long-term monitoring. Owing to some requirements for use in clinical practice, a GFR estimation method such as the Cockcroft-Gault, MDRD, CKD-EPI, and the Japanese Society of Nephrology's GFR estimation formula has been developed that is simple, inexpensive, and provides rapid results. However, an important clinical question is whether they can be used as a method of GFR evaluation in patients with cancer. When designing a drug dosing regimen in consideration of kidney function, it is important to make a comprehensive judgment, recognizing that there are limitations regardless of which estimation formula is used or if GFR is directly measured. Although CTCAEs are commonly used as criteria for evaluating kidney disease-related adverse events that occur during anticancer drug therapy, a specialized approach using KDIGO criteria or other criteria is required when nephrologists intervene in treatment. Each drug is associated with the different disorders related to the kidney. And various risk factors for kidney disease associated with each anticancer drug therapy.

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  • Chapter 2:indications and dosing of anticancer drug therapy in patients with impaired kidney function, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022. Reviewed

    Hiroyuki Nishiyama, Takamitsu Inoue, Yuichi Koizumi, Yusuke Kobayashi, Hiroshi Kitamura, Kazuhiro Yamamoto, Takashi Takeda, Takehito Yamamoto, Ryohei Yamamoto, Takeshi Matsubara, Junichi Hoshino, Motoko Yanagita

    International journal of clinical oncology   28 ( 10 )   1298 - 1314   2023.10

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    This comprehensive review discusses the dosing strategies of cancer treatment drugs for patients with impaired kidney function, specifically those with chronic kidney disease (CKD), undergoing hemodialysis, and kidney transplant recipients. CKD patients often necessitate dose adjustments of chemotherapeutic agents, e.g., platinum preparations, pyrimidine fluoride antimetabolites, antifolate agents, molecularly targeted agents, and bone-modifying agents, to prevent drug accumulation and toxicity due to diminished renal clearance of the administered drugs and their metabolites. In hemodialysis patients, factors such as drug removal from hemodialysis and altered pharmacokinetics demand careful optimization of anticancer drug therapy, including dose adjustment and timing of administration. While free cisplatin is removed by hemodialysis, most of the tissue- and protein-bound cisplatin remains in the body and rebound cisplatin elevations are observed after hemodialysis. It is not recommended hemodialysis for drug removal, regardless of timing. Kidney transplant patients encounter unique challenges in cancer treatment, as maintaining the balance between reduction of immunosuppression, switching to mTOR inhibitors, and considering potential drug interactions with chemotherapeutic agents and immunosuppressants are crucial for preventing graft rejection and achieving optimal oncologic outcomes. The review underscores the importance of personalized, patient-centric approaches to anticancer drug therapy in patients with impaired kidney function.

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  • Significance of pharmacist intervention to oral antithrombotic therapy in the pharmaceutical outpatient clinic of cardiovascular internal medicine: a retrospective cohort study. Reviewed International journal

    Tomoko Kurimura, Kazuhiro Yamamoto, Hidekazu Tanaka, Takayoshi Toba, Takeshi Kimura, Yasushi Habu, Kotaro Itohara, Yumi Kitahiro, Tomohiro Omura, Ikuko Yano

    Journal of pharmaceutical health care and sciences   9 ( 1 )   28 - 28   2023.9

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    BACKGROUND: Optimised antithrombotic therapy requires clinical experience and an understanding of the current guidelines. This retrospective study aimed to evaluate whether pharmacist interviews and interventions with patients taking oral antithrombotic drugs in the pharmaceutical outpatient cardiology clinic had favourable clinical outcomes including decreased bleeding. METHODS: The participants included patients visiting the outpatient clinic of cardiovascular internal medicine at the Kobe University Hospital from January-December 2017, and were taking oral antithrombotic medication. The observation period was from the first visit to the outpatient clinic to October 2021 or death. Patients who received pharmacist intervention more than twice were defined as the pharmacist intervention group. Two control patients per one pharmacist intervention group individual were selected from the non-intervention pool matched for age, gender and antithrombotic medication type. RESULTS: Of the 895 eligible patients, 132 were in the pharmacist intervention group and 264 were selected for the matched non-intervention group. Bleeding events according to the Bleeding Academic Research Consortium criteria over type 2 were significantly lower in the pharmacist intervention group compared with the non-intervention group (17.4% versus 28.4%, P = 0.019). There were no significant differences in mortality and heart failure hospitalisation frequency, stroke, or cardiovascular events between the groups. Multivariate analysis identified age (≥ 65 years) and pharmacist intervention as factors associated with bleeding (odds ratio = 2.29 and 0.51, respectively). CONCLUSION: Pharmacist intervention in the outpatient clinic of cardiovascular internal medicine was effective in reducing the risk of bleeding in patients undergoing antithrombotic therapy.

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  • A model-based pharmacokinetic assessment of drug–drug interaction between tacrolimus and nirmatrelvir/ritonavir in a kidney transplant patient with COVID-19 Reviewed

    Takeshi Tomida, Kotaro Itohara, Kazuhiro Yamamoto, Takeshi Kimura, Kohei Fujita, Atsushi Uda, Yumi Kitahiro, Naoki Yokoyama, Yoji Hyodo, Tomohiro Omura, Ikuko Yano

    Drug Metabolism and Pharmacokinetics   2023.9

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    DOI: 10.1016/j.dmpk.2023.100529

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  • 非がん性疼痛を有する患者のオピオイド使用状況モニタリングにおける薬剤師介入の効果 Reviewed

    飯田 真之, 大村 友博, 志田 有里, 番匠 咲帆, 大本 暢子, 山下 和彦, 槇本 博雄, 山本 和宏, 矢野 育子

    日本緩和医療薬学雑誌   16 ( 3 )   65 - 71   2023.9

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    神戸大学医学部附属病院では,緩和ケアチーム担当薬剤師がWHO方式がん疼痛治療法の鎮痛薬リストの強オピオイド鎮痛薬が処方された入院患者をモニタリングしている.今回,非がん性疼痛患者への強オピオイド使用に際して,薬剤師が検出した緩和薬物療法に関する薬物関連問題(Drug Related Problem,以下DRP)とその転帰について後方視的評価を行った.解析対象患者82名のうち47名(57.3%)にDRPを検出し,うち31名に対して病棟薬剤師を介して介入を行った結果,27名のDRPが解消された.初回モニタリング時に検出し,介入したDRPとしては,ガイドラインからみた不適切使用・禁忌(15件)や,適応のない薬剤の選択(18件)が多かった.緩和ケアチーム薬剤師が非がん性疼痛に対するオピオイド処方患者を一元的にモニタリングすることで,DRPを効率的に検出し,その解消につながる可能性がある.(著者抄録)

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  • Luteolin Protects Against 6-Hydoroxydopamine-Induced Cell Death via an Upregulation of HRD1 and SEL1L. Reviewed International journal

    Hiroki Nishiguchi, Tomohiro Omura, Ayaka Sato, Yumi Kitahiro, Kazuhiro Yamamoto, Junichi Kunimasa, Ikuko Yano

    Neurochemical research   2023.8

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    Parkinson's Disease (PD) is caused by many factors and endoplasmic reticulum (ER) stress is considered as one of the responsible factors for it. ER stress induces the activation of the ubiquitin-proteasome system to degrade unfolded proteins and suppress cell death. The ubiquitin ligase 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation 1 (HRD1) and its stabilizing molecule, the suppressor/enhancer lin-12-like (SEL1L), can suppress the ER stress via the ubiquitin-proteasome system, and that HRD1 can also suppress cell death in familial and nonfamilial PD models. These findings indicate that HRD1 and SEL1L might be key proteins for the treatment of PD. Our study aimed to identify the compounds with the effects of upregulating the HRD1 expression and suppressing neuronal cell death in a 6-hydroxydopamine (6-OHDA)-induced cellular PD model. Our screening by the Drug Gene Budger, a drug repositioning tool, identified luteolin as a candidate compound for the desired modulation of the HRD1 expression. Subsequently, we confirmed that low concentrations of luteolin did not show cytotoxicity in SH-SY5Y cells, and used these low concentrations in the subsequent experiments. Next, we demonsrated that luteolin increased HRD1 and SEL1L mRNA levels and protein expressions. Furthermore, luteolin inhibited 6-OHDA-induced cell death and suppressed ER stress response caused by exposure to 6-OHDA. Finally, luteolin did not reppress 6-OHDA-induced cell death when expression of HRD1 or SEL1L was suppressed by RNA interference. These findings suggest that luteolin might be a novel therapeutic agent for PD due to its ability to suppress ER stress through the activation of HRD1 and SEL1L.

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  • Upfront Use of First-/Second-Generation EGFR-TKI Followed by Osimertinib Shows Better Prognosis than Upfront Osimertinib Therapy in Japanese Patients with Non-small-cell Lung Cancer with Exon 19 Deletion: A Single-Center Retrospective Study Reviewed

    Tomoki Hori, Kazuhiro Yamamoto, Takefumi Ito, Shigeki Ikushima, Tomohiro Omura, Ikuko Yano

    Biological and Pharmaceutical Bulletin   46 ( 6 )   788 - 795   2023.6

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    DOI: 10.1248/bpb.b22-00794

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  • Association of Alpha-Actinin-3 Polymorphism With Sarcopenia in Kidney Transplant Recipients. Reviewed International journal

    Takuya Fujimoto, Yoji Hyodo, Takeshi Ishimura, Yuki Tashiro, Takahito Endo, Shun Nisioka, Naoki Yokoyama, Kazuhiro Yamamoto, Ikuko Yano, Masato Fujisawa

    Transplantation proceedings   55 ( 4 )   824 - 828   2023.5

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    BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and function and is associated with increased mortality. Certain genetic polymorphisms represent risk factors used to assess the incidence of sarcopenia; however, few studies have evaluated the association between genetic polymorphisms and sarcopenia after kidney transplantation (KTx). We examined single-nucleotide polymorphisms (SNPs) in the genes involved in sarcopenia after KTx. METHODS: Sixty-five patients who underwent KTx were enrolled in this study. We used the psoas mass index (PMI; the cross-sectional area of the bilateral psoas muscle/height) as a surrogate marker for assessing the extent of sarcopenia. We determined the PMI before KTx and 1 year after KTx, and we identified 5 SNPs in 5 genes associated with sarcopenia in the general population. Finally, the link between the changes in PMI 1 year after KTx and each SNP was examined. RESULTS: The median PMI before KTx and 1 year after KTx was 7.4 (4.6-13.2) and 7.0 (3.6-13.6), respectively. The PMI decreased in 43 patients (66.2%). The alpha-actinin-3 rs1815739 genotype was associated with changes in PMI; the distribution of CT+TT genotypes in the PMI decrease group was significantly higher than that of the CC genotype (odds ratio, 4.23; 95% CI 0.05-0.97; P = 0.025). Moreover, the T allele frequency was significantly higher in the PMI decrease group than in the PMI increase group (odds ratio, 2.34; 95% CI 0.18-0.950; P = 0.025). CONCLUSION: The alpha-actinin-3 rs1815739 genotype may represent a genetic risk factor for sarcopenia after KTx.

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  • Association of STAT3, CYP3A5, and ABCG2 Polymorphisms With Osimertinib-induced Adverse Events in NSCLC Patients. Reviewed International journal

    Masaaki Tanda, Kazuhiro Yamamoto, Tomoki Hori, Hiroki Nishiguchi, Miki Yagi, Michiko Shimizu, Toru Konishi, Tomonori Ozaki, Natsue Yoshioka, Motoko Tachihara, Takefumi Ito, Shigeki Ikushima, Tomohiro Omura, Ikuko Yano

    Anticancer research   43 ( 4 )   1775 - 1783   2023.4

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    BACKGROUND/AIM: Osimertinib is a key drug for treating epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Genetic differences may be associated to adverse events (AEs) induced by osimertinib. This retrospective observational multicenter study evaluated the association of genotypes, including STAT3 -1697C>G, CYP3A5 6986A>G, and ABCG2 421C>A, with the incidence of osimertinib-induced AEs in patients with EGFR mutation-positive NSCLC. PATIENTS AND METHODS: A total of 85 patients treated with osimertinib (Institution A: 33 patients, Institution B: 52 patients) were enrolled in the study. Single nucleotide polymorphisms were determined by real-time PCR, and the incidence of AEs was compared for each genotype. RESULTS: Paronychia incidence was 59% for the CC genotype, 19% for the CG genotype, and 19% for the GG genotype at STAT3 -1697C>G. A genotype-related trend was observed (Cochran-Armitage test, p=0.009). Multivariate analysis showed that the CC genotype at STAT3 -1697C>G and female sex were significant independent factors associated with paronychia [odds ratio (OR)=6.41, 95% confidence interval (CI)=1.94-21.20 and OR=3.40, 95%CI=1.03-11.22, respectively]. The incidence of diarrhea was 53% for the CC genotype, 30% for the AC genotype, and 29% for the AA genotype at ABCG2 421C>A, and a genotype-related trend was observed (p=0.048). However, the CC genotype at ABCG2 421C>A was not a significant independent factor associated with diarrhea in multivariate analysis. No significant associations were detected between other polymorphisms and the incidence of AEs. CONCLUSION: STAT3 -1697C>G may be a novel risk factor for osimertinib-induced paronychia in patients with NSCLC.

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  • ALBI Grade Is a Predictive Factor of Lenvatinib Treatment Discontinuation due to Adverse Events in Hepatocellular Carcinoma. Reviewed International journal

    Daichi Enomoto, Kazuhiro Yamamoto, Yuki Matsumoto, Asami Morioka, Tomohiro Omura, Shohei Komatsu, Yoshihiko Yano, Takumi Fukumoto, Ikuko Yano

    Anticancer research   43 ( 3 )   1317 - 1323   2023.3

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    BACKGROUND/AIM: Lenvatinib is a multiple-tyrosine kinase inhibitor used to treat hepatocellular carcinoma (HCC), and its systematic concentration varies according to liver function. The albumin-bilirubin (ALBI) grade is a novel indicator for predicting liver function in patients with hepatic disease. This study aimed to investigate the relationship between ALBI grade and HCC patients' lenvatinib treatment duration. PATIENTS AND METHODS: This is a retrospective cohort study of patients with HCC and Child-Pugh A treated with lenvatinib between April 2018 and December 2019. The baseline liver function was determined using the ALBI grade. The primary outcome was discontinuation owing to adverse events. The risk factors for discontinuation owing to adverse effects were analyzed using logistic regression. RESULTS: This investigation included 48 HCC patients. Patients with ALBI grade 2 had a significantly shorter time of discontinuation due to adverse events than those with grade 1 (p=0.036). However, the time of treatment failure did not differ between the groups. Multiple logistic regression analysis showed that ALBI grade 2 and non-use of antihypertensive drugs were independent factors for discontinuation due to adverse events [odds ratio (OR)=14.1, 95% confidence interval (CI)=1.46-135, p=0.022 and OR=5.48, 95% CI=1.13-23.9, p=0.024, respectively]. CONCLUSION: The ALBI grades may be useful in predicting adverse events caused by lenvatinib in patients with HCC and Child-Pugh A.

    DOI: 10.21873/anticanres.16279

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  • Physiologically-based pharmacokinetic model to investigate the effect of pregnancy on risperidone and paliperidone pharmacokinetics: Application to a pregnant woman and her neonate. Reviewed International journal

    Walaa Y B Mahdy, Kazuhiro Yamamoto, Takahiro Ito, Naoko Fujiwara, Kazumichi Fujioka, Tadasu Horai, Ikuo Otsuka, Hitomi Imafuku, Tomohiro Omura, Kazumoto Iijima, Ikuko Yano

    Clinical and translational science   16 ( 4 )   618 - 630   2023.1

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    This study aimed to determine the effects of pregnancy and ontogeny on risperidone and paliperidone pharmacokinetics by assessing their serum concentrations in two subjects and constructing a customized physiologically-based pharmacokinetic (PBPK) model. Risperidone and paliperidone serum concentrations were determined in a pregnant woman and her newborn. PBPK models for risperidone and paliperidone in adults, pediatric, and pregnant populations were developed and verified using the Simcyp simulator. These models were then applied to our two subjects, generating their "virtual twins." Effects of pregnancy on both drugs were examined using models with fixed pharmacokinetic parameters. In the neonatal PBPK simulation, 10 different models for estimating the renal function of neonates were evaluated. Risperidone was not detected in the serum of both pregnant woman and her newborn. Maternal and neonatal serum paliperidone concentrations were between 2.05-3.80 and 0.82-1.03 ng/ml, respectively. Developed PBPK models accurately predicted paliperidone's pharmacokinetics, as shown by minimal bias and acceptable precision across populations. The individualized maternal model predicted all observed paliperidone concentrations within the 90% prediction interval. Fixed-parameter simulations showed that CYP2D6 activity largely affects risperidone and paliperidone pharmacokinetics during pregnancy. The Flanders metadata equation showed the lowest absolute bias (mean error: 22.3% ± 6.0%) and the greatest precision (root mean square error: 23.8%) in predicting paliperidone plasma concentration in the neonatal population. Our constructed PBPK model can predict risperidone and paliperidone pharmacokinetics in pregnant and neonatal populations, which could help with precision dosing using the PBPK model-informed approach in special populations.

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  • Efficacy and Long-Term Safety of Ibuprofen Gargle for Oral Lichen Planus: A Study Protocol of Randomized Crossover and Long-Term Extension Trials Reviewed

    Yumi Kitahiro, Takeshi Ioroi, Yasumasa Kakei, Junya Yamashita, Akira Kimoto, Takumi Hasegawa, Asami Morioka, Kazuhiro Yamamoto, Masaya Akashi, Ikuko Yano

    Methods and Protocols   6 ( 1 )   7 - 7   2023.1

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    Oral lichen planus (OLP) is a type of chronic and refractory stomatitis characterized by abnormal keratinization, which is often painful. There is no consensus regarding treatment options for OLP, particularly in the presence of pain. The current study protocol focuses on the short-term efficacy and long-term safety of an ibuprofen gargle for pain management in patients with OLP. Patients (n = 24) with painful OLP will be enrolled. During a crossover study period, patients in the ibuprofen–placebo (IP) group will receive an ibuprofen gargle (0.6%) on day 1, a placebo gargle on day 2, and an ibuprofen gargle on days 3–5 at least once daily. Patients in the placebo–ibuprofen (PI) group will receive a placebo gargle on day 1, an ibuprofen gargle on day 2, and an ibuprofen gargle on days 3–5 at least once daily. The primary endpoint of the crossover study period is the change in pain level as measured by a visual analogue scale score from before gargle administration to 5 min after gargle administration on days 1 and 2. The primary endpoint of the long-term extension study is assessment of long-term safety. The results of this study may support existing evidence regarding the effectiveness of ibuprofen rinses in treating OLP.

    DOI: 10.3390/mps6010007

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  • 抗がん薬調製ロボット導入前後における薬剤師のがん薬物療法関連業務の比較 Reviewed

    伊藤 雄大, 丹田 雅明, 水田 直美, 丸上 奈穂, 山口 由加里, 植田 梨沙, 梅山 遥, 伊藤 恵, 山本 和宏, 槇本 博雄, 大村 友博, 矢野 育子

    日本病院薬剤師会雑誌   58 ( 6 )   627 - 632   2022.6

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    神戸大学医学部附属病院では、2019年8月より抗がん薬調製ロボット(以下、調製ロボット)の日常業務での運用を開始した。そこで、調製ロボット導入前後の評価期間として2019年5~7月および2020年8~10月の各3ヵ月間を設定し、薬剤師のがん薬物療法関連業務を比較した。調製ロボット導入後に抗がん薬調製総件数は有意に増加したが、調製ロボットの調製率は調製総件数の29.2%を占め、薬剤師による抗がん薬調製件数は導入前に比べて導入後に有意に減少した(1,653±51 vs.1,330±20件/月、平均値±標準偏差、p<0.01)。また、薬剤師の対患者業務に関して、初回抗がん薬治療時の治療説明件数は導入前後で35±10件/月から55±5件/月へと有意に増加した(p=0.04)。調製ロボットの導入は、薬剤師による調製件数の減少とそれに伴うマンパワーの対患者業務へのシフトに有用である。(著者抄録)

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J04451&link_issn=&doc_id=20220606220006&doc_link_id=%2Fdg4hppha%2F2022%2F005806%2F006%2F0627-0632%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg4hppha%2F2022%2F005806%2F006%2F0627-0632%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Safety and Efficacy of Bis-Glyceryl Ascorbate as Prophylaxis for Hand-Foot Skin Reaction: A Single-Arm, Open-Label Phase I/II Study (DGA Study). Reviewed International journal

    Kazuhiro Yamamoto, Satoshi Nishiyama, Makoto Kunisada, Masashi Iida, Takahiro Ito, Takeshi Ioroi, Hiroo Makimoto, Tomohiro Omura, Kenichi Harada, Masato Fujisawa, Chikako Nishigori, Ikuko Yano

    The oncologist   27 ( 5 )   e384-e392   2022.5

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    Abstract

    Background

    Hand-foot skin reaction (HFSR) induced by multiple tyrosine kinase inhibitors (TKIs) is a serious side effect that can cause treatment interruption or decreased dosing. This study was conducted to evaluate the safety and efficacy of bis-glyceryl ascorbate (Amitose bis(di)-glyceryl ascorbate [DGA])-containing cream (DGA cream) for the prevention of sunitinib-induced HFSR.

    Methods

    A single-arm, open-label phase I/II study was conducted, targeting patients with metastatic renal cell carcinoma (mRCC) who were receiving sunitinib therapy with a schedule of 2 weeks on/1 week off. The participants applied DGA cream to both palmar and plantar surfaces in combination with a moisturizing agent as standard-of-care prophylaxis during two sunitinib treatment cycles (6 weeks). The primary endpoint in phase I was safety defined as dermatological abnormalities and it was determined in the first five participants. The primary endpoint in phase II was efficacy defined as development of grade 1 or higher HFSR defined by Common Terminology Criteria for Adverse Events within 6 weeks and it was determined on a full analysis set (FAS) defined as the population including all participants who used DGA cream once in the study duration. Efficacy in the per protocol set (PPS) defined as the population excluding seven patients whose study treatment was interrupted was evaluated as a secondary endpoint.

    Results

    Twenty-four patients were enrolled as a FAS. No dermatological abnormalities occurred in the first 5 patients enrolled in the phase I study. Three patients developed HFSR (grade 1: n = 2, grade 2: n = 1) in the observation period. The HFSR incidence rate was 12.5% (3/24; 95% confidence interval [CI]: 2.7%-32.4%) in the FAS, which was significantly lower than the incidence rate predefined as a threshold of 33.3% by a previous report from our hospital (P = .030). The incidence rate in the 17 patients of the PPS was 17.6% (3/17; 95%CI: 3.8%-43.4%).

    Conclusion

    DGA cream may be safe and effective in the prophylaxis of HFSR in mRCC patients who receive sunitinib therapy (Trial ID: jRCTs051180051).

    DOI: 10.1093/oncolo/oyab067

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  • STAT3 Polymorphism Associates With mTOR Inhibitor-Induced Interstitial Lung Disease in Patients With Renal Cell Carcinoma. Reviewed International journal

    Kazuhiro Yamamoto, Takeshi Ioroi, Kazuaki Shinomiya, Ayaka Yoshida, Kenichi Harada, Masato Fujisawa, Tomohiro Omura, Yasuaki Ikemi, Shunsaku Nakagawa, Atsushi Yonezawa, Osamu Ogawa, Kazuo Matsubara, Takuya Iwamoto, Kohei Nishikawa, Sayaka Hayashi, Daichi Tohara, Yoji Murakami, Takanobu Motoshima, Hirofumi Jono, Ikuko Yano

    Oncology research   29 ( 1 )   11 - 23   2022.5

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    We evaluated the association of signal transducer and activator of transcription 3 (STAT3) polymorphisms with the incidence of mammalian target of rapamycin (mTOR) inhibitor-induced interstitial lung disease (ILD) in patients with renal cell carcinoma (RCC). We also used lung-derived cell lines to investigate the mechanisms of this association. Japanese patients with metastatic RCC who were treated with mTOR inhibitors were genotyped for the STAT3 polymorphism, rs4796793 (1697C/G). We evaluated the association of the STAT3 genotype with the incidence of ILD and therapeutic outcome. In the 57 patients included in the primary analysis, the ILD rate within 140 days was significantly higher in patients with the GG genotype compared with those with other genotypes (77.8% vs. 23.1%, odds ratio=11.67, 95% confidential interval=3.0644.46). There were no significant differences in progression-free survival or time-to-treatment failure between the patients with the GG genotype and those with other genotypes. An in vitro study demonstrated that some lung-derived cell lines carrying the GG genotype exhibited an increase in the expression of mesenchymal markers, such as fibronectin, N-cadherin, and vimentin, and decreases in E-cadherin, which is an epithelial marker associated with exposure to everolimus, although STAT3 expression and activity were not related to the genotype. In conclusion, the GG genotype of the STAT3 rs4796793 polymorphism increases the risk of mTOR inhibitor-induced ILD, supporting its use as a predictive marker for RCC.

    DOI: 10.3727/096504022X16418911579334

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  • Effectiveness of pharmacist intervention for deprescribing potentially inappropriate medications: a prospective observational study. Reviewed International journal

    Takeshi Kimura, Misa Fujita, Michiko Shimizu, Kasumi Sumiyoshi, Saho Bansho, Kazuhiro Yamamoto, Tomohiro Omura, Ikuko Yano

    Journal of pharmaceutical health care and sciences   8 ( 1 )   12 - 12   2022.4

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    Abstract

    Background

    Potentially inappropriate medications (PIMs) and polypharmacy in older adults lead to increase the risk of adverse drug events. This study aimed to evaluate the effectiveness of pharmacist intervention combining the criteria for detecting PIMs with the deprescribing algorithm on correcting PIMs, reducing the number of medications, and readmissions.

    Methods

    A prospective observational study was conducted at a Japanese University Hospital enrolling new inpatients aged ≥65 years prescribed ≥1 daily medication. Pharmacists detected PIMs based on the criteria combined the screening tool of older persons’ potentially inappropriate prescriptions criteria version 2 with the screening tool for older persons’ appropriate prescriptions for Japanese, examined changes using the deprescribing algorithm, and suggested changes to the physician. The proportion of patients whose number of medications was reduced at discharge and the rate of readmissions within 30 and 90 days were compared between patients without PIMs (without PIMs group), patients who were not suggested to change PIMs (no suggestions group), and patients who were suggested to change PIMs (suggested group).

    Results

    The study enrolled 544 patients (median age 75.0 years, 54.4% males, median number of medications 6.0/patient). The number of patients with PIMs was 240 (44.1%), and 304 patients had no PIMs (without PIMs group). Among the patients with PIMs, 125 (52.1%) patients received pharmacist suggestions to change ≥1 PIMs (suggested group), and 115 patients received no suggestions for change (no suggestions group). The total number of PIMs was 432, of which changes were suggested for 189 (43.8%). Of these 189 cases, 172 (91.0%) were changed. The proportion of patients whose number of medications was reduced was significantly higher in the suggested group than in the without PIMs group and the no suggestions group [56.8% (71/125) vs. 26.6% (81/304) and 19.1% (22/115), respectively; P &lt; 0.001 in both comparisons]. There were no significant differences in the rates of readmissions within 30 and 90 days among the three groups.

    Conclusions

    Pharmacist intervention combining the criteria for detecting PIMs with the deprescribing algorithm was effective for correcting PIMs and may be associated with a reduction in the number of medications.

    DOI: 10.1186/s40780-022-00243-0

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    Other Link: https://link.springer.com/article/10.1186/s40780-022-00243-0/fulltext.html

  • Association of sunitinib concentration and clinical outcome in patients with metastatic renal cell carcinoma treated with a 2-week-on and 1-week-off schedule. Reviewed International journal

    Takahiro Ito, Kazuhiro Yamamoto, Junya Furukawa, Kenichi Harada, Masato Fujisawa, Tomohiro Omura, Ikuko Yano

    Journal of clinical pharmacy and therapeutics   47 ( 1 )   81 - 88   2022.1

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    WHAT IS KNOWN AND OBJECTIVE: Sunitinib is used as a first-line therapy for metastatic renal cell carcinoma. The primary aim of this study was to determine the optimal total sunitinib (sunitinib plus N-desethyl sunitinib) trough concentration for the alternative dosing schedule: 2-week-on and 1-week-off schedule (2/1 schedule). METHODS: Patients with metastatic renal cell carcinoma treated with the 2/1 schedule of sunitinib, whose total sunitinib concentrations were available, were recruited for this study. Out of 19 patients, 17 whose sunitinib dosage was not changed until the measurement of drug concentration were eligible for the analysis of the relationship between total sunitinib concentration and clinical outcome. Individual pharmacokinetic parameters in 19 patients were estimated via the Bayesian analysis. RESULTS: The onset of severe (grade ≥3) adverse effects among 17 patients during 3 weeks as a first course of sunitinib therapy was observed in 7 (41.2%) patients. The median total sunitinib concentration in patients with severe adverse effects was significantly higher compared with that in patients without severe adverse effects [median: 119 (113-131) vs. 87.8 (77.4-102) ng/mL, p = 0.01]. According to the receiver operating characteristic analysis of the onset of severe adverse effects, the cut-off value of the total sunitinib concentration was 108 ng/mL. Patients with a total sunitinib concentration lower than 108 ng/mL had a longer time to first dose reduction or withdrawal due to adverse effects compared with those with a total sunitinib concentration of 108 ng/mL or higher (p = 0.03). The probability without treatment failure was not significantly different between the two concentration groups. In addition, the estimated sunitinib apparent oral clearance (CL/F) was significantly lower in the severe adverse effects group. Our simulation demonstrated that 0.67-time dose is needed for patients with approximately 90.0 ng/mL of sunitinib concentration on day 7 to maintain the concentration at the same level as the patients with higher CL/F. WHAT IS NEW AND CONCLUSION: Maintaining the total sunitinib trough concentrations of less than 108 ng/mL is safe to avoid the onset of serious adverse effects without increasing the treatment failure in patients with metastatic renal cell carcinoma treated with the 2/1 schedule of sunitinib.

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  • Effects of Proton Pump Inhibitors on Survival Outcomes in Patients with Metastatic or Unresectable Urothelial Carcinoma Treated with Pembrolizumab. Reviewed

    Yoko Kunimitsu, Kayoko Morio, Sachi Hirata, Kazuhiro Yamamoto, Tomohiro Omura, Takuto Hara, Kenichi Harada, Masato Fujisawa, Ikuko Yano

    Biological & pharmaceutical bulletin   45 ( 5 )   590 - 595   2022

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    The gut microbiome influences tumor response to immune checkpoint inhibitors (ICIs). The proton pump inhibitors (PPI) significantly impair diversity of the gut microbiota and can affect the efficacy of ICIs. Therefore, the present study aimed to evaluate the influence of PPI on survival in patients with metastatic or unresectable urothelial carcinoma receiving pembrolizumab. We conducted a retrospective cohort study of patients with metastatic or unresectable urothelial carcinoma receiving pembrolizumab. The use of PPI was defined as any administration for ≥30 d within 60 d prior and/or 30 d after treatment initiation. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and Cox proportional hazards regression analysis was performed to investigate prognostic factors based on patient characteristics. Seventy-nine patients were included in the analysis, and 34 patients (43.0%) received PPI. There were no significant differences in OS and PFS between PPI users and nonusers (median OS: 8.2 months vs. 11.2 months, hazard ratio (HR): 1.36, 95% confidence interval (CI): 0.75-2.42, p = 0.296; median PFS: 3.5 months vs. 5.1 months, HR: 1.63, 95% CI: 0.95-2.80, p = 0.069). In the multivariable analysis, PPI use was not associated with OS (HR 0.80, 95% CI 0.40-1.56, p = 0.526) or PFS (HR 1.44, 95% CI 0.79-2.60, p = 0.233). In conclusion, the estimated effect size of PPI use on survival in Japanese patients with metastatic or unresectable urothelial carcinoma treated with pembrolizumab was not reproducible.

    DOI: 10.1248/bpb.b21-00939

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  • Induction of Cross-resistance to ABCB1 Substrates in Venetoclax-resistant Human Leukemia HL60 Cells. Reviewed International journal

    Yuko Nakayama, Kohji Takara, Tetsuya Minegaki, Kazuhiro Yamamoto, Tomohiro Omura, Ikuko Yano

    Anticancer research   41 ( 9 )   4239 - 4248   2021.9

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    BACKGROUND/AIM: Resistance to venetoclax, a selective inhibitor of BCL2 apoptosis regulator (BCL2), is regarded as a clinical problem. However, it is unclear whether resistance to venetoclax induces cross-resistance to other drugs. MATERIALS AND METHODS: Venetoclax-resistant HL60/VEN cells were newly established through continuous exposure of human acute promyelocytic leukemia HL60 cells to venetoclax, and drug sensitivity, apoptotic activity, and mRNA expression were compared between HL60 and HL60/VEN cells. RESULTS: HL60/VEN cells displayed approximately 3-fold resistance to venetoclax, maintained their ability to synthesize DNA and had low apoptotic activity. HL60/VEN cells also exhibited diverse sensitivity to cytotoxic drugs, especially resistance to ATP binding cassette subfamily B member 1 (ABCB1) substrates, and up-regulation of ABCB1 mRNA. However, the sensitivity of HL60/VEN cells to venetoclax was not restored by ABCB1 inhibitor. ABCB1-overexpressing cells did not show resistance to venetoclax. CONCLUSION: HL60/VEN cells exhibited up-regulation of ABCB1 in addition to an alteration in apoptotic activity, and cross-resistance to ABCB1 substrates was clarified. However, sensitivity to venetoclax was hardly affected by ABCB1.

    DOI: 10.21873/anticanres.15228

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  • Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan. Reviewed International journal

    Jumpei Saito, Naomi Nadatani, Makoto Setoguchi, Masahiko Nakao, Hitomi Kimura, Mayuri Sameshima, Keiko Kobayashi, Hiroaki Matsumoto, Naoki Yoshikawa, Toshihiro Yokoyama, Hitomi Takahashi, Mei Suenaga, Ran Watanabe, Kinuko Imai, Mami Obara, Mari Hashimoto, Kazuhiro Yamamoto, Naoko Fujiwara, Wakako Sakata, Hiroaki Nagai, Takeshi Enokihara, Sayaka Katayama, Yuta Takahashi, Mariko Araki, Kanako Iino, Naoko Akiyama, Hiroki Katsu, Kumiko Fushimi, Tomoya Takeda, Mayumi Torimoto, Rina Kishi, Naoki Mitsuya, Rie Kihara, Yuki Hasegawa, Yukihiro Hamada, Toshimi Kimura, Masaki Wada, Ayano Tanzawa, Akimasa Yamatani

    Journal of pharmaceutical health care and sciences   7 ( 1 )   23 - 23   2021.7

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    BACKGROUND: A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted. METHODS: A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE. RESULTS: Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified. CONCLUSIONS: Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.

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  • Relationship Between Tramadol Response and Cancer Cachexia: A Retrospective Cohort Study. Reviewed International journal

    Kayoko Morio, Kazuhiro Yamamoto, Ikuko Yano

    The American journal of hospice & palliative care   38 ( 3 )   276 - 282   2021.3

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    OBJECTIVE: It was reported that the administration of tramadol in patients with cancer pain who have a higher interleukin 6 (IL-6) serum level led to insufficient pain relief. Cytokines produced by tumors, including IL-6, are associated with cancer cachexia. However, whether nonresponse to tramadol is related to cancer cachexia is unknown. The purpose of this study was to examine the relationship between tramadol response and cancer cachexia in patients with cancer pain. METHODS: We conducted a retrospective cohort study of patients with cancer who received tramadol treatment for mild to moderate pain from January 2016 to June 2019. Patients who experienced <20% pain reduction based on the numeric rating scale from baseline to day 7 after treatment with tramadol were defined as nonresponders. Univariate and multivariate logistic regression analyses were conducted to examine the relationships between tramadol response and various patient characteristics, including cancer cachexia. RESULTS: Of 115 patients, 79 were included in the analysis. A total of 24 patients experienced cancer cachexia, and 22 patients were nonresponders. In the univariate logistic analysis, cancer cachexia (odds ratio [OR]: 6.04, 95% confidence interval [CI]: 2.06-17.7), higher white blood cell counts (× 103/μL; OR: 1.28, 95% CI: 1.04-1.61), and lower body mass index (OR: 0.79, 95% CI: 0.66-0.96) were significantly associated with nonresponse to tramadol. The multivariate logistic analysis revealed that cancer cachexia (OR: 5.27, 95% CI: 1.75-15.9) was the only significant factor associated with nonresponse to tramadol. CONCLUSIONS: Cancer cachexia in patients with cancer pain can be associated with nonresponse to tramadol.

    DOI: 10.1177/1049909120945570

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  • Sunitinib decreases the expression of KRT6A and SERPINB1 in 3D human epidermal models. Reviewed International journal

    Ayaka Yoshida, Kazuhiro Yamamoto, Takahiro Ishida, Tomohiro Omura, Tomoo Itoh, Chikako Nishigori, Toshiyasu Sakane, Ikuko Yano

    Experimental dermatology   30 ( 3 )   337 - 346   2021.3

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    Hand-foot skin reaction (HFSR) is a common side effect caused by several tyrosine kinase inhibitors, including sunitinib. However, the nature of the cornifying factors related to the molecular biological mechanisms underlying HFSR remains poorly understood. We used human keratinocyte models to investigate the key cornifying factors for dermatological and biological abnormalities induced by sunitinib. On the basis of the results of microarray analysis using the three-dimensional (3D) human epidermal model, keratin (KRT)6A, serine protease inhibitor (SERPIN)B1, KRT5, and SERPIN Kazal-type 6 were selected as candidate genes related to HFSR. Sunitinib treatment significantly decreased the expression of SERPINB1 and KRT6A in the immunohistochemical staining of the 3D epidermal model. In PSVK1 cells, but not in normal human epidermal keratinocyte cells, both of which are human normal keratinocyte cell lines, sunitinib decreased the expression of KRT6A with a concomitant decrease in levels of phosphorylated extracellular signal-regulated kinases (ERK)1/2 and phosphorylated p38 mitogen-activated protein kinase (MAPK). Inhibitors of the ERK and p38 MAPK signal pathways also significantly decreased KRT6A expression. Sunitinib-induced decrease in KRT6A expression was suppressed by the inhibition of glycogen synthase kinase-3β by enhancing ERK1/2 and p38 MAPK phosphorylation. Thus, sunitinib reduces the expression of KRT6A and SERPINB1 by inhibiting the ERK1/2 and p38 MAPK signalling pathways in the skin model. These changes in expression contribute to the pathology of HFSR.

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  • MicroRNA-101 Regulates 6-Hydroxydopamine-Induced Cell Death by Targeting Suppressor/Enhancer Lin-12-Like in SH-SY5Y Cells. Reviewed International journal

    Tomohiro Omura, Luna Nomura, Ran Watanabe, Hiroki Nishiguchi, Kazuhiro Yamamoto, Satoshi Imai, Shunsaku Nakagawa, Kotaro Itohara, Atsushi Yonezawa, Takayuki Nakagawa, Junichi Kunimasa, Ikuko Yano, Kazuo Matsubara

    Frontiers in molecular neuroscience   14   748026 - 748026   2021

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    Endoplasmic reticulum (ER) stress has been reported as a cause of Parkinson's disease (PD). We have previously reported that the ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1) and its stabilizing factor suppressor/enhancer lin-12-like (SEL1L) participate in the ER stress. In addition, we recently demonstrated that neuronal cell death is enhanced in the cellular PD model when SEL1L expression is suppressed compared with cell death when HRD1 expression is suppressed. This finding suggests that SEL1L is a critical key molecule in the strategy for PD therapy. Thus, investigation into whether microRNAs (miRNAs) regulate SEL1L expression in neurons should be interesting because relationships between miRNAs and the development of neurological diseases such as PD have been reported in recent years. In this study, using miRNA databases and previous reports, we searched for miRNAs that could regulate SEL1L expression and examined the effects of this regulation on cell death in PD models created by 6-hydroxydopamine (6-OHDA). Five miRNAs were identified as candidate miRNAs that could modulate SEL1L expression. Next, SH-SY5Y cells were exposed to 6-OHDA, following which miR-101 expression was found to be inversely correlated with SEL1L expression. Therefore, we selected miR-101 as a candidate miRNA for SEL1L modulation. We confirmed that miR-101 directly targets the SEL1L 3' untranslated region, and an miR-101 mimic suppressed the 6-OHDA-induced increase in SEL1L expression and enhanced cell death. Furthermore, an miR-101 inhibitor suppressed this response. These results suggest that miR-101 regulates SEL1L expression and may serve as a new target for PD therapy.

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  • 経口抗がん薬治療における情報共有ツールおよびチーム基盤型学習を用いた病診薬連携の有用性の評価 Reviewed

    植田 梨沙, 丹田 雅明, 伊藤 雄大, 榎本 彩花, 飯田 真之, 水田 直美, 山本 和宏, 槇本 博雄, 大村 友博, 矢野 育子

    医療薬学   46 ( 12 )   681 - 691   2020.12

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  • Model-based assessment of pharmacokinetic changes of sunitinib, tacrolimus, and everolimus in a patient with metastatic renal cell carcinoma after renal transplantation. Reviewed International journal

    Takahiro Ito, Kazuhiro Yamamoto, Satoshi Ogawa, Junya Furukawa, Kenichi Harada, Masato Fujisawa, Tomohiro Omura, Ikuko Yano

    Drug metabolism and pharmacokinetics   35 ( 5 )   405 - 409   2020.10

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    The safety of the coadministration of sunitinib with tacrolimus and everolimus with regard to therapeutic drug monitoring has not been demonstrated. Here, we report a patient who showed high sunitinib concentrations, in addition to pharmacokinetic changes in tacrolimus and everolimus after sunitinib therapy. A living-donor renal transplant patient treated with tacrolimus and everolimus was diagnosed with pulmonary and pleural metastases of renal cell carcinoma. The patient received sunitinib therapy (37.5 mg/day, 2 weeks on and 1 week off). This patient exhibited a high total sunitinib concentration (sunitinib, 105.8 ng/mL; N-desethyl sunitinib, 27.9 ng/mL) on day 10 postinitiation and experienced grade 3 diarrhea. The observed sunitinib concentrations were a little higher than those reported in the 421C>A polymorphism of the ATP-binding cassette subfamily G member 2 gene carrier. The observed concentrations of both tacrolimus and everolimus gradually decreased compared with the Bayesian-predicted values after the onset of sunitinib therapy, and the doses of tacrolimus and everolimus were increased. Careful therapeutic drug monitoring of sunitinib, tacrolimus, and everolimus concentrations is necessary during combination therapy, especially after episodes of diarrhea.

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  • PETINIA法による血中ミコフェノール酸測定試薬の基準測定法LC-MS/MS法との比較 Reviewed

    大籔 智奈美, 佐藤 伊都子, 山本 和宏, 矢野 育子, 中町 祐司, 三枝 淳

    医学検査   69 ( 1 )   36 - 43   2020.1

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    ミコフェノール酸モフェチル(mycophenolate mofetil;MMF)は臓器移植において主に用いられている免疫抑制薬で、ミコフェノール酸(mycophenolic acid;MPA)のプロドラッグである。MPAのAUC0-12が臨床効果や拒絶反応に相関することから、薬物血中濃度モニタリング(therapeutic drug monitoring;TDM)が推奨されている。血漿中MPA濃度測定には従来LC-MS/MS法やEMIT法などが用いられていたが、前者は操作が煩雑で多大な時間を要すること、後者は代謝産物との交差反応により偽高値を示す可能性があることが知られている。今回、PETINIA法による血漿中MPA測定試薬の基本性能および各種検体条件による影響について検討するとともに、高濃度領域も含めたLC-MS/MS法との相関性について評価した。PETINIA法によるMPA血中濃度測定は、感度や再現性、特異性において良好な性能を示した。血清分離剤による測定値への影響は認められず、保存安定性は試薬添付文書上の期間内で保たれていた。LC-MS/MS法との相関は良好であるが(y=1.18x-0.09、r=0.980、p<0.01)、15μg/mL以上の高濃度領域ではPETINIA法が高値を示すことが明らかとなった。以上より、PETINIA法による血漿中MPA濃度測定は低濃度領域では臨床的に有用性であるが、高濃度領域においては、解釈に注意が必要であることが示唆された。(著者抄録)

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  • Ibuprofen gargle for chemo- or Chemoradiotherapy-induced Oral Mucositis: a feasibility study. Reviewed International journal

    Takeshi Ioroi, Naomi Kiyota, Yoshinori Imamura, Masaaki Tanda, Shiori Aoki, Mamoru Okuno, Kazuhiro Yamamoto, Ryohei Sasaki, Ken-Ichi Nibu, Hironobu Minami, Midori Hirai, Ikuko Yano

    Journal of pharmaceutical health care and sciences   6   12 - 12   2020

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    Background: Oral mucositis frequently occurs in cancer patients treated with chemotherapy and chemoradiotherapy (CRT). This study examined the safety and efficacy of ibuprofen gargle in healthy volunteers and patients with chemotherapy- and concomitant CRT-induced oral mucositis. Methods: We enrolled healthy volunteers and patients with chemotherapy- and CRT-induced oral mucositis. In cohort I, single and multiple doses of ibuprofen gargle (0.6% or 1.0%) were administered to healthy volunteers on day 1 and days 4-10. In cohort II, multiple doses of ibuprofen gargle (0.6%) were administered to patients with complicated grade 2-3 oral mucositis based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The primary endpoint of cohort I was the treatment-related adverse events (TRAEs) as defined by CTCAE version 4.0. The primary endpoint of cohort II was the change in the visual analogue scale (VAS) pain score from before to 15 min after gargle use on day 3. The incidence and severity of TRAEs were assessed based on the CTCAE version 4.0 and a subjective rating scale completed by healthy volunteers and patients. Results: In cohort I, 9 of 10 healthy volunteers were evaluable for safety. All 9 healthy volunteers reported the TRAE of oral irritation with single or multiple use of the gargle. In cohort II, 10 patients were enrolled and evaluable for safety and 7 of 10 patients were evaluable for efficacy. The mean change in the VAS pain score from before to 15 min after using the gargle on day 3 was - 1.28 (95% confidence interval: - 2.06, - 0.51), and all patients experienced some degree of pain relief (range: - 0.2 to - 2.5). All 10 patients reported the TRAE of oral irritation. No other TRAEs of ibuprofen gargle were observed in the healthy volunteers and patients. Conclusion: Despite oral irritation, the ibuprofen gargle appeared to be safe and effective for the pain related to chemo- or CRT-induced oral mucositis. However, ibuprofen-related oral irritation warrants further formulation improvement. Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000014433).

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  • 疑義照会における検査値連動型の処方チェックシステムの有用性 Reviewed

    冨田 猛, 山本 和宏, 山下 和彦, 大本 暢子, 槇本 博雄, 矢野 育子

    医療薬学   45 ( 12 )   698 - 705   2019.12

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    疑義照会における腎機能以外の電解質等の検査値も含めた処方チェックシステムの有用性について評価した。調査期間は2009年6〜11月の6ヵ月間(検査値印字未実施期間;I群)、2010年6〜11月の6ヵ月間(検査値印字実施期間;II群)、2016年9月〜2017年8月の12ヵ月間(チェックシステム導入期間;III群)とした。検査値を根拠とした疑義照会による処方変更件数は1ヵ月あたりI群が0件(0%)、II群が13.8件(6.6%)、III群が22.7件(8.9%)であり、II群と比べてIII群で有意に増加した。変更となった処方の内訳はII群では腎機能関連が最も多かったが、III群では電解質関連の占める割合が大きく増加した。薬剤別では、III群における腎機能関連の疑義照会のうち、レボフロキサシン、ファモチジン、レボセチリジン、セフカペン等が多かった。

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  • Pharmacokinetic assessment of alprazolam-induced neonatal abstinence syndrome using physiologically based pharmacokinetic model. Reviewed International journal

    Kazuhiro Yamamoto, Sachiyo Fukushima, Yui Mishima, Mari Hashimoto, Kei Yamakawa, Kazumichi Fujioka, Kazumoto Iijima, Ikuko Yano

    Drug metabolism and pharmacokinetics   34 ( 6 )   400 - 402   2019.12

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    Sustained benzodiazepine use during pregnancy can induce neonatal abstinence syndrome (NAS). In this study, the association between NAS and plasma alprazolam concentration was examined using the measured neonatal concentrations in the time series as well as simulated plasma concentrations of pregnant woman and neonate by physiologically based pharmacokinetic (PBPK) modeling. A neonate born to a mother taking alprazolam daily throughout pregnancy exhibited symptoms such as apnea and vomiting from 9 h to 4 days after birth. Finnegan score was 7 at birth and decreased to 0 by day 4. Apnea improved by 24 h post-delivery and gastrointestinal symptoms disappeared by day 4. The plasma alprazolam concentration in the neonate was 15.2 ng/mL immediately after birth and gradually decreased over 3 days. Measured neonate and estimated maternal plasma alprazolam concentrations were within the 90% prediction intervals of each concentration by PBPK simulation using "pregnancy" and "pediatrics" population parameters including in Simcyp population-based ADME simulator. In conclusion, NAS symptoms such as apnea and digestive events disappeared in parallel with the decrease of the neonate's plasma alprazolam concentrations. Moreover, PBPK modeling and simulation is a useful methodology for toxicological assessment in special characteristics populations lacking specific experimental data.

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  • Efficacy of pharmacists’ assessment and intervention based on Screening Tool for Older Persons’ Appropriate Prescriptions for Japanese compared with Screening Tool of Older Persons' potentially inappropriate Prescriptions criteria version 2 in older patients with cardiovascular disease. Reviewed

    Takeshi Kimura, Fumie Ogura, Yukiko Kukita, Tomoko Takahashi, Kazuhiro Yamamoto, Takeshi Ioroi, Ikuko Yano

    Geriatrics & gerontology international   19 ( 11 )   1101 - 1107   2019.11

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    AIM: This study aimed to evaluate the efficacy of pharmacists' assessment and intervention using the Screening Tool for Older Persons' Appropriate Prescriptions for Japanese (STOPP-J) to detect and correct potentially inappropriate medications (PIM) compared with the Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP) criteria version 2. METHODS: A prospective observational study was carried out at a medical unit of Cardiovascular Surgery and Cardiovascular Internal Medicine in a Japanese university hospital involving new inpatients aged ≥65 years prescribed one or more daily medication. Pharmacists detected PIM based on STOPP-J and STOPP criteria version 2, and corrected them with physicians. The number of patients with PIM, the content and changes in PIM were compared between both criteria. RESULTS: Overall, 230 patients were included (mean age 75.4 years, 162 men, mean number of medications 8.3). STOPP-J detected significantly more patients with PIM than STOPP criteria version 2 (122 [53%] vs 75 [33%], P < 0.001). The number of PIM based on STOPP-J was 232, the physicians were recommended to change 61 (26%) and 50 (22%) were changed. Meanwhile, the number of PIM based on STOPP criteria version 2 was 133, the physicians were recommended to change 61 (46%) and 54 (41%) were changed. Several medications detected as PIM using STOPP-J were not detected using STOPP criteria version 2. CONCLUSIONS: STOPP-J detected significantly more patients with PIM than STOPP criteria version 2, and pharmacists' assessment and intervention based on STOPP-J were suggested to be effective for detecting and correcting PIM. Geriatr Gerontol Int 2019; 19: 1101-1107.

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  • オピオイド服用患者における酸化マグネシウムの緩下作用に対してプロトンポンプ阻害薬併用が与える影響 Reviewed

    岡田 美咲, 飯田 真之, 伊藤 雄大, 五百蔵 武士, 山本 和宏, 矢野 育子

    日本病院薬剤師会雑誌   55 ( 8 )   964 - 968   2019.8

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    胃酸分泌抑制剤の併用により酸化マグネシウム(magnesium oxide:以下、MgO)の効果が減弱することが報告されている。本研究では、オピオイド服用患者における便秘改善に要したMgO投与量に対するプロトンポンプ阻害薬(proton pump inhibitor:以下、PPI)併用の影響について調査した。対象は、神戸大学医学部附属病院緩和ケアチームが介入し、モルヒネまたはオキシコドンを定時内服している患者37名とした。便秘改善に要したMgO投与量は、PPI併用群、非併用群ともに平均約20mg/kg/dayであり、有意差は認められなかった。しかし、65歳未満の患者における便秘改善に要したMgO投与量は、PPI併用群で非併用群と比べて有意に多かった(27.4±10.2mg/kg/day vs 19.2±2.5mg/kg/day、p=0.03)。以上、65歳未満の非高齢患者においてはPPIの併用がMgOの効果減弱に寄与する可能性がある。(著者抄録)

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J04451&link_issn=&doc_id=20190805190012&doc_link_id=%2Fdg4hppha%2F2019%2F005508%2F012%2F0964-0968%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg4hppha%2F2019%2F005508%2F012%2F0964-0968%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Safety and Efficacy of Bis-Glyceryl Ascorbate (Amitose DGA) to Prevent Hand-Foot Skin Reaction in Patients With Renal Cell Carcinoma Receiving Sunitinib Therapy: Protocol for a Phase I/II, Uncontrolled, Single-Arm, Open-Label Trial Reviewed

    Yamamoto Kazuhiro, Ioroi Takeshi, Harada Kenichi, Nishiyama Satoshi, Nishigori Chikako, Yano Ikuko

    JMIR Research Protocols   8 ( 8 )   e14636   2019.8

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    Background: Hand-foot skin reaction (HFSR) is a serious side effect induced by multiple-tyrosine kinase inhibitors (TKIs). HFSR can cause treatment interruption or decreased dosing. HFSR also markedly decreases quality of life and is associated with the therapeutic efficacy of multiple-TKIs. Therefore, the management and prevention of HFSR is an important issue; however, an effective method for its prevention has not been established. Specific ascorbic acid derivatives can reverse multiple-TKI-induced keratinocyte growth and pathological changes in vitro. Objective: This study was designed to evaluate the safety of bis-glyceryl ascorbate (Amitose DGA), a novel, hydrosoluble, and moisturizing ascorbic acid derivative, in patients with renal cell carcinoma (RCC) receiving sunitinib therapy. This study was also designed to evaluate Amitose DGA's preventive efficacy for sunitinib-induced HFSR. Methods: This is a Phase I/II, single-center, uncontrolled, single-arm, open-label trial. We will recruit a total of 30 patients with RCC receiving sunitinib therapy, with a 2-week-on and 1-week-off schedule. The participants will apply Amitose DGA-containing cream over both palmar and plantar surfaces within two treatment cycles (ie, 6 weeks) of sunitinib in combination with a general moisturizing agent, in addition to standard-of-care processes. Safety assessments will include dermatological abnormalities, clinical laboratory tests, and incidence of adverse events. Efficacy assessments will include development of HFSR and therapeutic outcomes associated with sunitinib. Results: Recruitment to the study began in August 2017 and is ongoing in Japan. To date, 21 subjects have been recruited. Study completion is expected in 2021. Conclusions: This is the first clinical study of Amitose DGA-containing cream in patients with RCC who are receiving sunitinib therapy. The single-center, single-arm, open-label design was selected to maximize subject exposure and increase the likelihood of achieving our study endpoints. The results will provide valuable and preliminary evidence of the effects of Amitose DGA-containing cream on HFSR.

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  • Bitterness-Masking Effects of Different Beverages on Zopiclone and Eszopiclone Tablets. Reviewed

    Miyako Yoshida, Honami Kojima, Atsushi Uda, Tamami Haraguchi, Minoru Ozeki, Ikuo Kawasaki, Kazuhiro Yamamoto, Ikuko Yano, Midori Hirai, Takahiro Uchida

    Chemical & pharmaceutical bulletin   67 ( 5 )   404 - 409   2019

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    The purpose of the study was to evaluate the ability of different beverages to mask the bitterness of zopiclone and eszopiclone in tablet formulations using the artificial taste sensor and human gustatory sensation testing. The beverages tested for bitterness-masking effects were: Mugicha, Sports beverage, Lactic acid drink, Orange juice and a diluted simple syrup (an 8.5% sucrose solution). The bitterness intensities estimated by the taste sensor of zopiclone or eszopiclone one-tablet solutions mixed with the various beverages, corresponded well with the observed bitterness intensities measured by gustatory sensation testing. The Sports beverage, Lactic acid drink and Orange juice significantly suppressed the bitterness intensity of both zopiclone and eszopiclone 1-tablet solutions compared with water when tested in the artificial taste sensor. Sports beverage, Lactic acid drink and Orange juice all contain citric acid as acidifier, so it was postulated that citric acid was involved in the mechanism of bitterness intensity suppression of zopiclone and eszopiclone 1-tablet solutions by these three beverages. It was then shown that citric acid suppressed the bitterness intensity of a zopiclone one-tablet sample solution in a dose-dependent manner. 1H-NMR spectroscopic analysis of mixtures of citric acid with zopiclone suggested that the carboxyl groups of citric acid interact with the amine group on zopiclone. This study therefore showed that the bitterness intensities of zopiclone and eszopiclone can be suppressed by citric-acid-contained beverages and suggests that this bitterness suppression is due to a direct electrostatic interaction between citric acid and the two drugs.

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  • 電気化学発光免疫測定法によるエベロリムス血中濃度測定試薬"エクルーシス試薬エベロリムス"の基礎的検討 Reviewed

    大籔 智奈美, 佐藤 伊都子, 東口 佳苗, 山本 和宏, 石村 武志, 中町 祐司, 三枝 淳

    医学検査   67 ( 5 )   722 - 726   2018.10

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    mTOR阻害薬であるエベロリムスは、臓器移植における免疫抑制剤として主に用いられている。エベロリムスの投与に関しては、急性拒絶反応に対する有効性、副作用に対する安全性から薬物血中濃度モニタリング(TDM)を定期的に行うことが必要である。全血中のエベロリムス濃度測定には、LC-MS/MS法が用いられていたが、操作が煩雑であるために臨床の日常業務における測定には不適当であった。近年、ラテックス免疫比濁法(LTIA法)を原理とする試薬が開発されたが、推奨トラフ値はLC-MS/MS法の測定値をもとに設定されており、測定法による値の差の評価が必要であると言われている。そこで今回、新たに開発された電気化学発光免疫測定法(ECLIA法)による「エクルーシス試薬エベロリムス」の基礎的検討を行った。ECLIA法による測定は再現性および感度が良好であり、LTIA法による測定値との相関は、y=1.24x+1.48(r=0.854)と良好であった。以上の結果から、ECLIA法はLTIA法による血中エベロリムス濃度の測定と同等以上の感度・精度を有することが確認され、エベロリムスのTDMに有用である可能性が示唆された。(著者抄録)

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  • PETINIA法による血中ミコフェノール酸測定試薬の基準測定法LC-MS/MS法との比較 Reviewed

    大籔 智奈美, 佐藤 伊都子, 山本 和宏, 中町 祐司, 三枝 淳

    臨床化学   47 ( Suppl.1 )   311 - 311   2018.7

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  • Association of Expression Levels or Activation Status of STAT3 with Treatment Outcomes of Sunitinib in Patients with Renal Cell Carcinoma Reviewed

    Kazuhiro Yamamoto, Takuto Hara, Tsutomu Nakagawa, Midori Hirai, Hideaki Miyake, Masato Fujisawa, Ikuko Yano

    Targeted Oncology   13 ( 3 )   371 - 378   2018.6

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    Background: The expression level of signal transducer and activator of transcription 3 (STAT3) in tumor cells is reported to associate with response to therapy and with survival time in various types of cancer. Objective: This retrospective study aimed to elucidate the association of STAT3 expression in tumor cells with the therapeutic outcomes of sunitinib in patients with renal cell carcinoma (RCC). Patients and Methods: Patients with metastatic RCC who received sunitinib therapy were enrolled in this study. All patients underwent nephrectomy for RCC, and nephrectomy specimens were stained for STAT3 and phosphorylated STAT3 (p-STAT3) by immunohistochemistry. Results: We assessed 51 patients receiving sunitinib as a first-line therapy. STAT3 expression levels did not influence progression-free survival (PFS) and overall survival (OS)
    however, patients with p-STAT3-positive tumors exhibited significantly worse PFS compared with those with p-STAT3-negative tumors (log-rank test, P = 0.034). OS tended to be prolonged in patients with p-STAT3-negative tumors. Objective response rate or disease control rate based on the best overall response did not show a significant association with STAT3 or p-STAT3 expression. Univariate Cox proportional hazard regression analyses for clinical predictors revealed that p-STAT3 positivity significantly correlated with shorter PFS (hazard ratio [HR], 2.22, P = 0.041), whereas p-STAT3 expression was not related to the OS. Conclusions: Activated STAT3 in tumor tissues shows a significant association with poor prognosis in patients with RCC who received sunitinib as a first-line therapy, and positive p-STAT3 expression could be a potential biomarker for refractoriness to sunitinib therapy. [Figure not available: see fulltext.].

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  • Association of the PCK2 Gene Polymorphism With New-onset Glucose Intolerance in Japanese Kidney Transplant Recipients Reviewed

    N. Yokoyama, T. Ishimura, T. Oda, S. Ogawa, K. Yamamoto, M. Fujisawa

    Transplantation Proceedings   50 ( 4 )   1045 - 1049   2018.5

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    Background: New-onset diabetes mellitus after transplantation (NODAT) is a risk factor for both cardiovascular disease and poor graft survival after kidney transplantation (KTx). In this study, we identified single-nucleotide polymorphisms (SNPs) in genes involved in glucose metabolism and examined the correlation between these SNPs and glucose intolerance after KTx. Methods: Thirty-eight patients with normal glucose tolerance before KTx were included in this study. Patients with plasma glucose levels of &gt
    140 mg/dL at 120 minutes on the 75-g oral glucose tolerance test at 1 year after KTx were classified as having new-onset impaired glucose tolerance (NIGT). We identified 8 SNPs in 7 genes that are involved in glucose metabolism among the patients included in this study, and compared the prevalence rate of NIGT among SNPs in each gene. Results: Of the 38 patients, 11 (28.9%) were diagnosed with NIGT. For rs4982856 in the PCK2 gene, the distribution of genotypes among the total patient population was as follows: T/T, 12 (31.6%)
    T/C, 22 (57.9%)
    and C/C, 4 (10.5%). Seven of 11 patients with NIGT had the T/T genotype of rs4982856, whereas only 5 of 27 patients with normal glucose tolerance had this genotype. The T allele frequency of the rs4982856 was significantly higher in the NIGT group than in the normal group (81.8 vs 52.8%, respectively
    P =.015). Conclusion: Our study indicates that the T allele of the rs4982856 SNP in the PCK2 gene may be a risk factor for glucose intolerance after KTx.

    DOI: 10.1016/j.transproceed.2018.01.042

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  • 薬剤師教育におけるチーム基盤型学習の有用性の検討 Reviewed

    伊藤 雄大, 高田 麻季, 飯田 真之, 宇田 篤史, 住吉 霞美, 秋山 恵里, 丸上 奈穂, 丹田 雅明, 野間 千尋, 山本 和宏, 五百蔵 武士, 木村 丈司, 西岡 達也, 久米 学, 槇本 博雄, 矢野 育子

    医療薬学   44 ( 5 )   236 - 243   2018.5

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    薬剤師歴が1〜8年目の薬剤師29名を対象とした。参加者を2群に分け、チーム基盤型学習(TBL)群と講義群に割り当てた。ジャーナルクラブの実施前に行ったプレテストのスコアと薬剤師歴、ジャーナルクラブに参加する前のモチベーションは、講義群とTBL群で有意差は認めなかった。ジャーナルクラブ参加前の予習時間は、TBL群において有意に短かった。主要評価項目であるプレテストとジャーナルクラブ直後のポストテストのスコア差は、講義群とTBL群で有意差は認めなかったが、プレテストのスコアで調整したプレテストとジャーナルクラブ直後のポストテストのスコア差は、TBL群で有意に高かった。ジャーナルクラブ直後のポストテストのスコアはTBL群で有意に高かった。ジャーナルクラブ1ヵ月後のポストテストのスコアは講義群とTBL群で有意差は認めないものの、TBL群においてスコアは高い傾向にあった。アンケートの結果、ジャーナルクラブに対する満足度は講義群とTBL群で有意差は認めなかった。TBLについてジャーナルクラブの満足度に対する顧客満足度分析を行い、重要維持項目は、「司会者の熱意」および「論文内容の解説」であった。

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  • Genetic polymorphisms associated with adverse reactions of molecular-targeted therapies in renal cell carcinoma Invited Reviewed

    Kazuhiro Yamamoto, Ikuko Yano

    Medical Oncology   35 ( 2 )   16   2018.2

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    The prognosis of patients with metastatic renal cell carcinoma has drastically improved due to the development of molecular-targeted drugs and their use in clinical practice. However, these drugs cause some diverse adverse reactions in patients and sometimes affect clinical outcomes of cancer therapy. Therefore, predictive markers are necessary to avoid severe adverse reactions, to establish novel and effective prevention methods, and to improve treatment outcomes. Some genetic factors involved in these adverse reactions have been reported
    however, perspectives on each adverse response have not been integrated yet. In this review, genetic polymorphisms relating to molecular-targeted therapy-induced adverse reactions in patients with renal cell carcinoma are summarized in the points of pharmacokinetic and pharmacodynamic mechanisms. We also discuss about the relationship between systemic drug exposure and adverse drug reactions.

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  • Association of CYP2D6 polymorphisms and extrapyramidal symptoms in schizophrenia patients receiving risperidone: a retrospective study. Reviewed International journal

    Ito T, Yamamoto K, Ohsawa F, Otsuka I, Hishimoto A, Sora I, Hirai M, Yano I

    Journal of pharmaceutical health care and sciences   4   28 - 28   2018

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    Background: Risperidone is mainly metabolized by cytochrome P450 (CYP) 2D6 in the liver. The gene encoding CYP2D6 is highly polymorphic. The average steady-state plasma concentration of risperidone active moiety is higher in the CYP2D6 intermediate metabolizers (IMs) compared with that in the extensive metabolizers (EMs). An association between drug-induced extrapyramidal symptoms scale (DIEPSS) score and CYP2D6 polymorphisms has not been reported to date. This study investigates the association of CYP2D6 polymorphisms with the severity of extrapyramidal symptoms in schizophrenia patients receiving risperidone therapy. Methods: Schizophrenia patients undergoing risperidone treatment were recruited for the study in the Kobe University Hospital. We evaluated extrapyramidal symptoms of schizophrenia using the DIEPSS. CYP2D6*10 and CYP2D6*14 were analyzed using TaqMan® assays, and CYP2D6*5 was analyzed using the long-PCR method. Patients with CYP2D6*1/*5, *1/*14, *5/*10, *10/*10, and *10/*14 were classified as IMs, and patients with CYP2D6*1/*1 and *1/*10 were classified as EMs. Patients with CYP2D6*5/*5, *5/*14, and *14/*14 were classified as poor metabolizers (PMs). Results: A total of 22 patients were included in the study. No patients were classified as PMs. The dose of risperidone (mg/day) was not significantly different between EMs (n = 15) and IMs (n = 7) (median with the interquartile range: 4.0 (2.0-6.0) vs. 4.0 (2.0-7.0) mg, p = 0.31). The age and disease duration of schizophrenia were not significantly different between the EMs and IMs. The DIEPSS score in the IMs was significantly higher than that in the EMs (median with the interquartile range: 5.0 (3.5-6.5) vs. 0.0 (0.0-3.0), p < 0.001). The multiple regression analysis showed that CYP2D6 IMs is a significant risk factor for the DIEPSS (p < 0.05). Conclusion: Special attentions should be paid to the onset of extrapyramidal symptoms in schizophrenia patients identified as CYP2D6 IM undergoing risperidone therapy.

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  • Effects of Ascorbyl-2-phosphate Magnesium on Human Keratinocyte Toxicity and Pathological Changes by Sorafenib Reviewed

    Kazuhiro Yamamoto, Hiroaki Shichiri, Takahiro Ishida, Kenta Kaku, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Toshinori Bito, Chikako Nishigori, Ikuko Yano, Midori Hirai

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   40 ( 9 )   1530 - 1536   2017.9

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    Hand foot skin reaction is recognized as one of the most common adverse events related to multiple tyrosine kinase inhibitors, but an effective prevention method has not been identified. The chief aim of this study was to find a mechanism-based preventive method for the skin toxicity induced by sorafenib using vitamin C derivatives. The effects of ascorbyl-2-phosphate magnesium (P-VC-Mg) on the molecular and pathological changes induced by sorafenib were investigated in human keratinocyte HaCaT cells. The cell growth inhibition and apoptotic effects of sorafenib were attenuated by P-VC-Mg. Moreover, P-VC-Mg inhibited the decrease of signal transducer and activator of transcription 3 (STAT3) phosphorylation and the expression of apoptosis suppressors treated by sorafenib. HaCaT cells transfected with the STAT3 dominant-negative form (STAT3DN) and STAT3 small interfering RNA (siRNA) combined with P-VC-Mg did not exhibit the attenuation of cell growth inhibition. Interestingly, after exposure to sorafenib in a three dimensional (3D) skin model assay, the basal layer was significantly thickened and the granular and spinous layers became thinner. In contrast, after exposure to sorafenib with P-VC-Mg, the thickness of the basal, granular, and spinous layers was similar to that of the control image. These findings suggest that P-VC-Mg attenuates sorafenibinduced apoptosis and pathological changes in human keratinocyte cells and in the 3D skin model mediated by the maintenance of STAT3 activity.

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  • Compatibility and Stability of Nab-Paclitaxel in Combination with Other Drugs. Reviewed

    Mizuta N, Nakagawa T, Yamamoto K, Nishioka T, Kume M, Makimoto H, Yano I, Minami H, Hirai M

    The Kobe journal of medical sciences   63 ( 1 )   E9 - E16   2017.7

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    DOI: 10.24546/81009873

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  • 日米の医薬品データベースの相互作用情報を迅速に検索できるシステムの構築と質疑への活用 Reviewed

    冨田 猛, 野崎 晃, 宇田 篤史, 山本 和宏, 西岡 達也, 久米 学, 槇本 博雄, 矢野 育子, 平井 みどり

    医薬品情報学   19 ( 1 )   1 - 7   2017.5

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    調査対象医薬品を、2016年4月現在の院内採用医薬品(採用医薬品)とし、本邦の相互作用情報について、添付文書の使用禁忌(原則禁忌も含む)、併用禁忌を調査対象項目として、MD bank(MB)を用い、MBおよびUp to Date(UD)における医薬品相互情報を収集し、一方ではあり、他方ではなしの組合せはないか比べ見出された課題を解消するツールとして、MBとUDの相互作用を迅速に検索できるシステムを構築し、情報収集と整合性の検討を行った。2016年4月現在の採用医薬品は内服薬739品目、外用薬254品目、注射薬637品目の合計1630品目であった。医薬品名検索で検索できなかった品目が305、うち採用医薬品と同一剤形の医薬品が検索できなかった品目が8あった。採用医薬品同士の医薬品相互作用の組合せ2655270通り中、MB、UDで相互作用の情報が収集できたのは329586組、MBでは使用禁忌と併用注意あわせて241270組の相互作用の情報収集ができた。

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  • Potentially inappropriate medications in elderly Japanese patients: effects of pharmacists' assessment and intervention based on Screening Tool of Older Persons' Potentially Inappropriate Prescriptions criteria ver.2 Reviewed

    T. Kimura, F. Ogura, K. Yamamoto, A. Uda, T. Nishioka, M. Kume, H. Makimoto, I. Yano, M. Hirai

    JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS   42 ( 2 )   209 - 214   2017.4

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    What is known and objectivesThe Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (stopp) criteria were updated in 2014 (stopp criteria ver.2), but few studies have evaluated the usefulness of stopp criteria in elderly patients. This prospective observational study evaluated the prevalence of potentially inappropriate medications (PIMs), and the efficacy of hospital pharmacists' assessment and intervention based on stopp criteria ver.2.
    MethodsThe study was conducted at three medical units of Kobe University Hospital between April 2015 and March 2016. Pharmacists assessed and detected PIMs based on stopp criteria ver.2 and considered the patient's intention to change the prescription at the time of admission of each patient. If the pharmacists judged that benefits outweighed risks of prescription change and the patients consented to change the medications, they recommended the doctor to change the prescription. If there was a risk of exacerbation of disease by the change of medications and the pharmacists judged it to be difficult to adjust medications during hospitalization or the patients did not consent to change the medications, they did not recommend to change it. The pharmacists and the doctors discussed and finally decided whether to change the PIMs or not. The number of patients prescribed PIMs, the number and contents of PIMs, and the number of medications changed after pharmacists' intervention were calculated.
    ResultsTotally, 822 new inpatients aged &gt;= 65 years prescribed &gt;= 1 daily medicine were included. Their median (interquartile range) age was 75.0 (71.0-80.0) years, and 54.9% were male. According to the criteria, 346 patients (42.1%) were prescribed &gt;= 1 PIMs. Patients prescribed PIMs took significantly more medications than others: 10.0 (7.0-13.0) vs. 60 (4.0-9.0), P &lt; 0001. The total number of PIMs was 651%, 47.6% of which (n = 310) were recommended the doctors to change, and 292 of 651 PIMs (44.9%) were finally discontinued/changed after pharmacists' assessment and intervention. PIMs related to benzodiazepines, including Z-drugs, were most frequent, with a detailed classifications as follows (changed/total): (i) benzodiazepines for 4 or more weeks (75/205), (ii) drugs that predictably increase the risk of falls in older people (benzodiazepines) (30/67) and (iii) drugs that predictably increase the risk of falls in older people (hypnotic Z-drugs) (15/31).
    ConclusionOver 40% elderly patients were prescribed PIMs, and pharmacists' assessments and interventions based on stopp criteria ver.2 were useful in detecting and correcting prescription of PIMs.

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  • Association of Single Nucleotide Polymorphisms in STAT3, ABCB1, and ABCG2 with Stomatitis in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib: A Retrospective Analysis in Japanese Patients Reviewed

    Aimi Watanabe, Kazuhiro Yamamoto, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Hideaki Miyake, Masato Fujisawa, Tsutomu Nakagawa, Ikuko Yano, Midori Hiraiab

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   40 ( 4 )   458 - 464   2017.4

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    Signal transducer and activator of transcription (STAT) 3 is a key factor in homeostasis of the oral mucosa by regulating the production of inflammatory cytokines. Sunitinib is a substrate of P-glycoprotein (multidrug resistance (MDR)-1/ABCB1) and breast-cancer resistance protein (BCRP/ABCG2). In this retrospective study, we evaluated the association between sunitinib-induced stomatitis and STAT3, ABCB1, and ABCG2 polymorphisms in patients with metastatic renal cell carcinoma (mRCC). Fifty-two Japanese patients with RCC treated with sunitinib were retrospectively genotyped to elucidate a potential association between STAT3, ABCB1, and ABCG2 polymorphisms and stomatitis development. Stomatitis occurred in 22 out of 52 patients. The TT+TC genotypes at STAT3 rs744166 had an odds ratio of 5.00 against CC genotype for the stomatitis development (95% confident interval, 0.97-25.8). In the Kaplan-Meier method for the cumulative incidence of stomatitis, a statistically significant difference was observed between the TT+TC and CC genotypes in STAT3 rs744166 (p=0.037). Both multiple logistic regression analysis and Cox proportional-hazards regression analysis show STAT3 rs744166 TT+TC genotypes and serum creatinine in each patient were significant independent factors for stomatitis development. In conclusion, STAT3 polymorphism may be a novel risk factor for sunitinib-induced stomatitis in patients with mRCC.

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  • Prostaglandin E-1 reduces the keratinocyte toxicity of sorafenib by maintaining signal transducer and activator of transcription 3 (STAT3) activity and enhancing the cAMP response element binding protein (CREB) activity Reviewed

    Hiroaki Shichiri, Kazuhiro Yamamoto, Maya Tokura, Takahiro Ishida, Atsushi Uda, Toshinori Bito, Chikako Nishigori, Tsutomu Nakagawa, Takeshi Hirano, Ikuko Yano, Midori Hirai

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   485 ( 2 )   227 - 233   2017.4

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    Hand-foot skin reaction (HFSR) is a common side effect of multiple tyrosine kinase inhibitors (mTKIs). HFSR can necessitate dose reductions or interruption of therapy owing to its negative effect on the quality of life. Therefore, effective use of mTKIs requires measures to prevent HFSR. We evaluated the effect of prostaglandin El (PGE(1)) on HFSR, because PGE(1) is already used to treat bed sores and skin ulcers and has established angiogenic and antiproliferative effects in keratinocytes. We found that the patho-genesis of sorafenib-induced HFSR is characterized by a decrease in levels of a phosphorylated signal transducer and activator of transcription 3 (STAT3). We investigated the effect of PGE(1) on the sorafenib-mediated reduction in phosphorylated STAT3 levels in HaCaT human epidermal keratinocytes. In cells treated with sorafenib, phosphorylated STAT3 levels decreased in a concentration-dependent manner, and this effect was blocked in cells treated with sorafenib and PGE(1). Furthermore, the expression of phosphorylated STAT3, the antiapoptotic proteins myeloid cell leukemia-1 (Mcl-1) and survivin decreased in cells pretreated with an inhibitor of CAMP response element binding protein (CREB). Cell viability increased in cells treated with sorafenib and PGE(1) compared with that in cells treated with sorafenib alone, and these effects were not observed in STAT3 knockdown HaCaT cells. Collectively, these findings indicate that PGE1 blocks the inhibitory effects of sorafenib on cell growth by maintaining the activity of STAT3 and enhancing the CREB activity. Therefore, PGE(1) might represent an effective treatment for the prevention of sorafenib-induced HFSR. (C) 2017 Elsevier Inc. All rights reserved.

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  • 「薬剤師外来」における薬学的処方介入とその評価 Reviewed

    栗村 朋子, 山本 和宏, 池田 剛久, 橋本 正良, 西岡 達也, 久米 学, 槇本 博雄, 矢野 育子, 平井 みどり

    医療薬学   43 ( 3 )   169 - 175   2017.3

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    「薬剤師外来」は、総合内科外来担当医1名と心臓血管外科外来担当医1名を対象に行い、薬剤師歴12年の薬剤師1名が専任で担当した。総合内科外来または心臓血管外科外来の「薬剤師外来」を受診した全ての患者を対象とした。「薬剤師外来」を受診した群(介入群)と比較するため、「薬剤師外来」を担当している医師と経験歴や専門領域が同様の総合内科医および心臓血管外科医各1名の外来を同一期間に受診した患者を非介入群とした。介入群は延べ517名であり、うち総合内科が338名、心臓血管外科が179名であった。介入群全体での中止および減量に関する処方変更件数および変更率は93件(18.0%)で、うち中止が64件(12.4%)、減量が29件(5.6%)であった。非介入群では、中止および減量が76件(10.1%)、うち中止が57件(7.6%)、減量が19件(2.5%)で、処方変更率はいずれも介入群が非介入群と比較して有意に高かった。介入群で中止・減量した薬剤に起因すると思われる症状の再発・再燃を5件認め、消化性潰瘍治療薬で3件、抗アレルギー薬で2件であった。非介入群では中止・減量に伴う有害事象の発現が6件あった。

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  • ゾピクロン錠とエスゾピクロン錠の苦味比較(第2報) ランダム化二重盲検クロスオーバー試験 Reviewed

    宇田 篤史, 大澤 史宜, 山本 和宏, 四宮 一昭, 平野 剛, 平井 みどり

    日本病院薬剤師会雑誌   53 ( 2 )   192 - 196   2017.2

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    超短時間型睡眠薬であるエスゾピクロン錠は、催眠活性の大部分を有するS体を抽出して開発されているため、ラセミ体であるゾピクロン錠に比べてより低用量で同等の催眠作用を有すると報告されている。一方、副作用である苦味について直接比較した検討は少ないが、承認時の臨床試験結果を比較した場合、ゾピクロン錠に比べてエスゾピクロン錠で報告が多いことが認められる。我々は前報で、錠剤を溶解した試験液ではゾピクロンがより強い苦味を有することを示したが、本研究では、内服後の評価を行うことを目的としてランダム化二重盲検クロスオーバー試験を実施した。その結果、ゾピクロン錠を内服した翌日でより強い苦味強度を示すとともに苦味が長く持続することが示された。この結果は、添付文書やインタビューフォームなどとは異なる結果となったが、医師や薬剤師が薬剤の選択や情報提供を行ううえで、より適切な根拠となる知見が得られたものと考える。(著者抄録)

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  • ゾピクロン錠とエスゾピクロン錠の苦味比較 Reviewed

    宇田 篤史, 吉田 都, 原口 珠実, 櫨川 舞, 水本 篤志, 山本 和宏, 平野 剛, 内田 享弘, 平井 みどり

    日本病院薬剤師会雑誌   52 ( 5 )   529 - 532   2016.5

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    現代の日本人における不眠症の有病率は、成人で約20%と言われている。睡眠治療にはベンゾジアゼピン系睡眠薬が主に使用されているが、より依存性が低い非ベンゾジアゼピン系睡眠薬として、ゾピクロン錠やエスゾピクロン錠が広く使用されている。両剤はともに味覚異常を示すことで知られているが、エスゾピクロン錠は、ラセミ体であるゾピクロンから、活性を有するS体のみを精製して開発されており、明確な違いは明らかではない。そこで本研究では、両剤の苦味を比較することを目的に検討を行った。その結果、苦味特異的な物質に反応を示す味覚センサ試験で、ゾピクロン錠がより強い苦味を示した。さらに健康成人を対象としたヒト官能試験でも、ゾピクロン錠でより強い苦味を示すことが認められた。本検討は薬剤の苦味強度を示すものであるが、エスゾピクロン錠に比べてゾピクロン錠がより強い苦味強度を有する可能性が示唆された。(著者抄録)

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  • STAT3 polymorphism rs4796793 may be a predictive factor of tumor response to multiple tyrosine kinase inhibitors in metastatic renal cell carcinoma in Japanese population Reviewed

    Kazuhiro Yamamoto, Takeshi Ioroi, Kazuya Kanaya, Kazuaki Shinomiya, Shiho Komoto, Sachi Hirata, Kenichi Harada, Aimi Watanabe, Manabu Suno, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Hideaki Miyake, Masato Fujisawa, Midori Hirai

    MEDICAL ONCOLOGY   33 ( 3 )   24   2016.3

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    Signal transducer and activator of transcription (STAT) 3 is a key factor in multiple tyrosine kinase inhibitor (mTKI)-induced growth inhibition and apoptosis of renal cell carcinoma (RCC) cells. This study aimed to identify associations between single-nucleotide polymorphisms (SNPs) in the STAT3 gene and tumor response to mTKIs in patients with metastatic RCC (mRCC). Seventy-one patients with clear cell RCC treated with any mTKI were retrospectively genotyped to elucidate a potential association between STAT3 SNPs and overall best response to drugs. Of 50 patients included for analysis, a partial or complete response was observed in 17. A significant association was found between rs4796793 alleles and tumor response [G vs. C, odds ratio (OR) 3.25, 95 % confidence interval (CI) 1.30-8.07]. There were a higher percentage of responders with the C/C genotype at rs4796793 than with the G/C + G/G genotypes (OR 4.46, 95 % CI 1.31-15.28). Time-to-event analysis demonstrated a statistically significant difference between patients with the CC genotype and those with G/C + G/G genotypes in time-to-treatment response, but not in progression-free survival or time-to-treatment failure. The rs4796793 genotype is a novel predictive factor of the response to mTKIs in patients with mRCC. However, prospective translational trials with larger patient cohorts are required to confirm these results.

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  • STOPP Criteriaを用いた高齢者のポリファーマシーに対する薬剤師による介入 Reviewed

    小倉 史愛, 木村 丈司, 宇田 篤史, 戸田 飛鳥, 赤澤 由子, 山本 和宏, 五百蔵 武士, 西岡 達也, 久米 学, 槇本 博雄, 平井 みどり

    医療薬学   42 ( 2 )   78 - 86   2016.2

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    STOPP Criteriaを用いた高齢者のポリファーマシーに対する薬剤師による介入について検討した。1剤以上使用中の薬剤がある65歳以上の新規入院患者201例(男性173名、女性128名、74.8±6.2歳)を対象とした。入院時持参薬の確認時に、STOPP Criteriaを用いて薬剤師が潜在的に不適切な処方(PIM)のスクリーニングを行った。STOPP Criteriaに該当した患者は81例で、非該当患者に比べ有意に服用薬剤数が多かった。STOPP Criteria該当患者では非該当患者に比べ有意に女性の割合が高く、年齢が高かった。服用薬剤数が多い患者群ほどSTOPP Criteria該当割合も増加する傾向が見られた。該当項目としてはNSAID、カルシウムチャネル拮抗薬、ベンゾジアゼピン系薬、βブロッカーに関連する項目が多く、これらの合計で全体の75%以上を占めた。STOPP Criteriaの65項目の内、該当のあった項目は23項目で全体の35.3%であった。該当したPIMは合計125件で、その内変更件数は35件であった。また積極的推奨件数は61件で、その内変更件数は32件であった。

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  • Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple Tyrosine Kinase Inhibitors: A Retrospective Analysis in Japanese Patients Reviewed

    Kazuhiro Yamamoto, Kazuaki Shinomiya, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Manabu Suno, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Toshinori Bito, Chikako Nishigori, Hideaki Miyake, Masato Fujisawa, Midori Hirai

    TARGETED ONCOLOGY   11 ( 1 )   93 - 99   2016.2

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    Signal transducer and activator of transcription (STAT)3 is a reported mediator of molecular-targeted drug-induced keratinocyte toxicity.
    Our purpose was to assess the association of single nucleotide polymorphisms (SNPs) in STAT3 with hand-foot skin reactions (HFSR) in patients with metastatic renal cell carcinoma (mRCC) treated with multiple tyrosine kinase inhibitors (mTKIs).
    Sixty-five Japanese patients with clear cell renal cell carcinoma who were treated with any mTKI at Kobe University Hospital were retrospectively genotyped to elucidate a potential association between STAT3 polymorphisms and HFSR development.
    The final analysis included 60 patients. HFSR was observed in 46 patients. The GG, GC, and CC genotypes at rs4796793 were found in 9, 27, and 24 patients, respectively. Three other STAT3 polymorphisms exhibited tight linkage disequilibrium with rs4796793. A significant association was found between the rs4796793 allele and HFSR [G vs. C; odds ratio [OR], 4.33; 95 % confidence interval [CI], 1.80-10.45; P = 0.001]. The GG genotype had the highest OR compared with GC + CC genotypes (OR, 10.75; 95 % CI, 2.38-48.07; P = 0.001). In a time-to-event Kaplan-Meier analysis, a statistically significant difference was observed between the GC + CC and the GG genotypes (P = 0.009).
    The rs4796793 genotype appears to be a novel factor for mTKI-induced HFSR in patients with mRCC. Prospective translational trials with larger numbers of patients are required to confirm our results. This research suggests a potential benefit of STAT3 polymorphism screening in patients treated with mTKIs

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  • Induction of Epithelial-Mesenchymal Transition via Activation of Epidermal Growth Factor Receptor Contributes to Sunitinib Resistance in Human Renal Cell Carcinoma Cell Lines Reviewed

    Atsushi Mizumoto, Kazuhiro Yamamoto, Yuko Nakayama, Kohji Takara, Tsutomu Nakagawa, Takeshi Hirano, Midori Hirai

    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS   355 ( 2 )   152 - 158   2015.11

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    Sunitinib is widely used for treating renal cell carcinoma (RCC). However, some patients do not respond to treatment with this drug. We aimed to study the association between sunitinib sensitivity and epithelial-mesenchymal transition (EMT) regulation via epidermal growth factor receptor (EGFR) signaling, which is a mechanism of resistance to anticancer drugs. Three RCC cell lines (786-O, ACHN, and Caki-1) were used, and then we evaluated cell viability, EMT regulatory proteins, and signal transduction with sunitinib treatment. Cell viability of 786-O cells was maintained after treatment with sunitinib. After treatment with sunitinib, EGFR phosphorylation increased in 786-O cells, resulting in an increase in the phosphorylation of extracellular signal-regulated kinase, nuclear translocation of beta-catenin, and expression of mesenchymal markers. These results suggest that sunitinib induced EMT via activation of EGFR in 786-O cells, but not in ACHN and Caki-1 cells. Caki-1/SN cells, a resistant cell line generated by continuous exposure to sunitinib, displayed increased phosphorylation of EGFR. Cell viability in the presence of sunitinib was decreased by erlotinib, as the selective inhibitor of EGFR, treatment in 786-O and Caki-1/SN cells. Similarly, erlotinib suppressed sunitinib-induced EGFR activation and upregulated mesenchymal markers. Thus, we postulate that resistance to sunitinib in RCC may be associated with EMT caused by activation of EGFR.

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  • Apoptotic Effects of the Extracts of Cordyceps militaris via Erk Phosphorylation in a Renal Cell Carcinoma Cell Line Reviewed

    Kazuhiro Yamamoto, Hiroaki Shichiri, Atsushi Uda, Kazuhiko Yamashita, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Midori Hirai

    PHYTOTHERAPY RESEARCH   29 ( 5 )   707 - 713   2015.5

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    Cordyceps militaris (CM) is gaining attention as a traditional medicinal food, but its molecular biological mechanisms for anti-cancer activity are not identified or clarified. We aimed to elucidate the synthesizing apoptotic effects of CM extracts and to determine the biological effects of CM extract against cordycepin alone in a renal cell carcinoma (RCC) cell line. CM extract showed higher effects of growth inhibition, apoptotic effect, and cell cycle arrest than cordycepin alone. Moreover, CM extract activated extracellular signal-regulated kinase (Erk) highly more than cordycepin alone. We suggest that cordycepin and CM extract induced apoptosis via the activation of Erk dominantly and AMP-activated protein kinase slightly; CM extract has more potent effects on apoptotic effects associated with Erk activation than cordycepin alone. Copyright (c) 2015 John Wiley & Sons, Ltd.

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  • Association of single nucleotide polymorphisms (SNP) in STAT3 gene with hand-foot skin reaction in metastatic renal cell carcinoma patients treated with multi-kinase inhibitor. Reviewed

    Kazuhiro Yamamoto, Takeshi Ioroi, Kazuaki Shinomiya, Sachi Hirata, Kenichi Harada, Manabu Suno, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Toshinori Bito, Chikako Nishigori, Hideaki Miyake, Masato Fujisawa, Midori Hirai

    JOURNAL OF CLINICAL ONCOLOGY   33 ( 15 )   2015.5

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  • Association of Toxicity of Sorafenib and Sunitinib for Human Keratinocytes with Inhibition of Signal Transduction and Activator of Transcription 3 (STAT3) Reviewed

    Kazuhiro Yamamoto, Atsushi Mizumoto, Kohji Nishimura, Atsushi Uda, Akira Mukai, Kazuhiko Yamashita, Manabu Kume, Hiroo Makimoto, Toshinori Bito, Chikako Nishigori, Tsutomu Nakagawa, Takeshi Hirano, Midori Hirai

    PLOS ONE   9 ( 7 )   e102110   2014.7

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    Hand-foot skin reaction is a most common multi-kinase inhibitor-related adverse event. This study aimed to examine whether the toxicity of sorafenib and sunitinib for human keratinocytes was associated with inhibiting signal transduction and activator of transcription 3 (STAT3). We studied whether STAT3 activity affects sorafenib-and sunitinib-induced cell growth inhibition in HaCaT cells by WST-8 assay. Stattic enhanced the cell-growth inhibitory and apoptotic effects of sorafenib and sunitinib. HaCaT cells transfected with constitutively-active STAT3 (STAT3C) were resistant to the sorafenib-and sunitinib-induced cell growth inhibition. STAT3 activity decreased after short-term treatment with sorafenib and sunitinib in a dose-dependent manner and recovered after long-term treatment with sorafenib and sunitinib at low doses. Moreover, the expression of survivin and bcl-2 decreased after treatment with sorafenib and sunitinib was concomitant with variations in STAT3 activity. Sorafenib-induced STAT3 inhibition was mediated by regulation via MAPK pathways in HaCaT cells, while sunitinib-induced STAT3 inhibition was not. Thus, STAT3 activation mediating apoptosis suppressors may be a key factor in sorafenib and sunitinib-induced keratinocyte cytotoxicity.

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  • 患者のジェネリック医薬品変更希望に影響を及ぼす患者背景・重要因子の探索 ジェネリック医薬品の適切な使用促進のために Reviewed

    四宮 一昭, 池方 康一郎, 小山 敏広, 山本 和宏, 平野 剛, 北村 佳久, 平井 みどり, 千堂 年昭

    日本薬剤師会雑誌   65 ( 11 )   1323 - 1325   2013.11

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    本調査研究では、ジェネリック医薬品(GE品)の使用促進を目的として、先発医薬品またはGE品の選択希望に関する実態調査を行い、患者のGE品変更希望に影響を与える重要因子の探索を試みた。調査では、2012年10月に処方箋を当薬局へ持参した患者全員を対象として、患者背景等の情報を抽出し、解析を行った。その結果、医薬品の処方剤数、ハイリスク薬処方、そして患者自己負担がGE品変更希望に対し影響を及ぼすことが示された。また、これらの患者背景及び因子が、患者のGE品選択希望に影響することを薬剤師が把握し、各患者の特徴や傾向に合わせてGE品の説明を行うことで、より効率的なGE品の使用促進につながると期待する。(著者抄録)

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  • Everolimus-induced human keratinocytes toxicity is mediated by STAT3 inhibition. Reviewed

    Yamamoto K, Uda A, Mukai A, Yamashita K, Kume M, Makimoto H, Bito T, Nishigori C, Hirano T, Hirai M

    Journal of experimental & clinical cancer research : CR   32 ( 1 )   83   2013.10

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    Background: Mammalian target of rapamycin (mTOR) inhibitors are associated with dermatological adverse events. The chief aim of this study was to examine the relation between the signal transducer and activator of transcription 3 (STAT3) protein and the dermatological adverse events associated with the mTOR inhibitor everolimus. Methods. We evaluated the effects of STAT3 activity and related signal transduction activities on everolimus-induced cell growth inhibition in the human keratinocyte HaCaT cell line via a WST-8 assay, and on signal transduction mechanisms involved in everolimus treatments via a western blot analysis. Apoptosis was evaluated using an imaging cytometric assay. Results: The cell growth inhibitory effects of everolimus were enhanced by stattic or STA-21, which are selective inhibitors of STAT3, treatment in HaCaT cells, although such effects were not observed in Caki-1 and HepG2 cells. Phosphorylation at tyrosine 705 of STAT3 was decreased by treatment with everolimus in a dose-dependent manner in HaCaT cells
    in contrast, phosphorylation at serine 727 was not decreased by everolimus, but slightly increased. Furthermore, we found that pretreatment of p38 MAPK inhibitor and transfection with constitutively active form of STAT3 in HaCaT cells resisted the cytostatic activity of everolimus. Conclusions: These findings suggest that STAT3 activity may be a biomarker of everolimus-induced dermatological toxicity. © 2013 Yamamoto et al.
    licensee BioMed Central Ltd.

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  • Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug resistance and transport in SN-38-resistant HeLa cells Reviewed

    Kohji Takara, Mika Matsubara, Kazuhiro Yamamoto, Tetsuya Minegaki, Shigehiko Takegami, Minoru Takahashi, Teruyoshi Yokoyama, Katsuhiko Okumura

    MOLECULAR MEDICINE REPORTS   5 ( 3 )   603 - 609   2012.3

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    The effects of 9 calcium antagonists on ABCG2/ BCRP-mediated resistance and transport were examined in He La and SN-38-resistant He La (HeLa/SN100) cells, over-expressing ABCG2/BCRP. Sensitivity to mitoxantrone, an ABCG2/BCRP substrate, in HeLa/SN100 cells was significantly reversed by the coexistence of the calcium antagonists, except for diltiazem and verapamil. The accelerated transport activity of Hoechst33342, an ABCG2/BCRP substrate, in HeLa/SN100 cells was significantly decreased by the presence of the calcium antagonists, except for diltiazem, nifedipine or verapamil, returning to the level of He La cells. The present study classifies the calcium antagonists into 3 categories: strong (benidipine, felodipine, nicardipine, nisoldipine and nitrendipine), moderate (amlodipine and nifedipine) and weak (diltiazem and verapamil) inhibitors of ABCG2/BCRP.

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  • Effects of alpha-Adrenoceptor Antagonists on ABCG2/BCRP-Mediated Resistance and Transport Reviewed

    Kohji Takara, Kazuhiro Yamamoto, Mika Matsubara, Tetsuya Minegaki, Minoru Takahashi, Teruyoshi Yokoyama, Katsuhiko Okumura

    PLOS ONE   7 ( 2 )   e30697   2012.2

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    Acquired resistance of cancer cells to various chemotherapeutic agents is known as multidrug resistance, and remains a critical factor in the success of cancer treatment. It is necessary to develop the inhibitors for multidrug resistance. The aim of this study was to examine the effects of eight alpha-adrenoceptor antagonists on ABCG2/BCRP-mediated resistance and transport. Previously established HeLa/SN100 cells, which overexpress ABCG2/BCRP but not ABCB1/MDR1, were used. The effects of the antagonists on sensitivity to mitoxantrone and the transport activity of Hoehst33342, both substrates for ABCG2/BCRP, were evaluated using the WST-1 assay and cellular kinetics, respectively. ABCG2/BCRP mRNA expression and the cell cycle were also examined by real-time RT-PCR and flow cytometry, respectively. Sensitivity to mitoxantrone was reversed by the alpha-adrenoceptor antagonists in a concentration-dependent manner, although such effects were also found in the parental HeLa cells. Levels of ABCG2/BCRP mRNA expression were not influenced by the antagonists. The transport activity of Hoechst33342 was decreased by doxazosin and prazosin, but unaffected by the other antagonists. In addition, doxazosin and prazosin increased the proportion of S phase cells in the cultures treated with mitoxantrone, whereas the other alpha-adrenoceptor antagonists increased the percentage of cells in G2/M phase. These findings suggested that doxazosin and prazosin reversed resistance mainly by inhibiting ABCG2/BCRP-mediated transport, but the others affected sensitivity to mitoxantrone via a different mechanism.

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  • Treatment schedule-dependent effect of 5-fluorouracil and platinum derivatives in colorectal cancer cells Reviewed

    Kohji Takara, Megumi Fujita, Tetsuya Minegaki, Kazuhiro Yamamoto, Minoru Takahashi, Teruyoshi Yokoyama, Katsuhiko Okumura

    EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES   45 ( 3 )   272 - 281   2012.2

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    Aim: Combination chemotherapy for treating cancer often is superior in clinical efficacy to monotherapy. The aim of this study was to investigate the schedule-dependent effect of 5-fluorouracil (5-FU) and platinum derivatives (cisplatin or oxaliplatin) in colorectal cancer (CRC) cell lines, and to explore factors affecting it.
    Methods: Two human CRC-derived cell lines, DLD-1 and HCT116, were used. Three treatment schedules were tested, and growth inhibitory effects were evaluated with a WST-1 assay. Combined effects were assessed with isobolograms and a combination index. Cellular accumulation and DNA-binding of platinum were measured with inductively coupled plasma mass spectrometry.
    Results: Exposure to 5-FU followed by cisplatin produced synergistic effects in DLD-1 cells, and the amount of platinum bound to DNA was substantially increased as compared with that for other schedules. 5-FU and oxaliplatin also tended to be synergistic when 5-FU was given first, but no significant change in the cellular kinetics of platinum was observed. On the other hand, in HCT116 cells, the combined effects of 5-FU and platinum derivatives were comparable among the three schedules.
    Conclusion: Exposure to 5-FU followed by cisplatin had a synergistic effect in DLD-1 cells, suggesting that the amount of platinum bound to DNA contributes to this result. Also, the effect was dependent on the type of platinum derivative and cell. (C) 2011 Elsevier B.V. All rights reserved.

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  • Role of the mTOR complex 1 pathway in the in vivo maintenance of the intestinal mucosa by oral intake of amino acids Reviewed

    Akira Nakamura, Kenta Hara, Kazuhiro Yamamoto, Hisafumi Yasuda, Hiroaki Moriyama, Midori Hirai, Masao Nagata, Koichi Yokono

    GERIATRICS & GERONTOLOGY INTERNATIONAL   12 ( 1 )   131 - 139   2012.1

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    Aim: Oral intake of nutrients is often compromised in elderly, multimorbid patients, but parenteral nutrition causes intestinal atrophy and impairs intestinal function. To uncover the molecular mechanisms by which amino acids are involved in intestinal atrophy and recovery, we studied whether the rapamycin-sensitive mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway is involved in this process.
    Methods: C57BL/6N mice were fed a glucose solution alone, glucose solution with amino acids or normal chow diet for various lengths of time. Intestinal sections were prepared from these mice and the villus height and villus density were quantified. As a readout for the mTORC1 pathway, the phosphorylation of the ribosomal S6 protein (S6) was analyzed by immunostaining and immunoblotting. To confirm the role of the mTORC1 pathway, the inhibitory effect of a specific mTOR inhibitor, rapamycin, was examined.
    Results: Inducing fasting in mice fed only glucose caused time-dependent intestinal mucosal atrophy, whereas supplementation with amino acids protected the intestinal mucosa from atrophy. Phosphorylation of S6 decreased in the intestinal mucosa of mice fed only glucose, whereas supplementation with amino acids increased S6 phosphorylation. Importantly, intraperitoneal injection of rapamycin attenuated the protective effect of amino acids on the intestinal mucosa in a pattern consistent with the decrease of S6 phosphorylation.
    Conclusions: These results indicate that the mTORC1 pathway plays a crucial role in the in vivo maintenance of the intestinal mucosa by the oral intake of amino acids. Geriatr Gerontol Int 2012; 12: 131-139.

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  • Characterization, in vitro cytotoxicity and cellular accumulation of paclitaxel-loaded lipid nano-emulsions Reviewed

    Shigehiko Takegami, Kohji Takara, Shiori Tanaka, Kazuhiro Yamamoto, Masahiro Hori, Teruyoshi Yokoyama, Tatsuya Kitade

    JOURNAL OF MICROENCAPSULATION   27 ( 5 )   453 - 459   2010.8

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    Lipid nano-emulsions (LNEs) having a mean droplet size of 50 nm were investigated as drug carriers for paclitaxel (TXL) to achieve its satisfactory loadings and to develop a pharmaceutically acceptable alternative to the current formulation, Taxol. TXL was incorporated into the LNEs at 2.0 mg/ml without changes in particle size or drug precipitation. In the cytotoxicity study, TXL-loaded LNEs had cytotoxicity to HeLa cells equivalent to that of TXL alone; the 50% growth inhibitory concentrations (IC50) of TXL-loaded LNEs and TXL alone were 1.53 +/- 0.23 nM and 1.76 0.08 nM, respectively. However, a cellular accumulation study using 1,6-dipheny1-1,3,5-hexatriene (DPH) as a fluorescent probe showed that the accumulation of DPH-loaded LNEs in HeLa cells was remarkably lower than that of DPH alone. These results indicated that LNEs were a useful vehicle for TXL, even though LNEs themselves could not be efficiently accumulated in HeLa cells.

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  • Molecular changes to HeLa cells on continuous exposure to SN-38, an active metabolite of irinotecan hydrochloride Reviewed

    Kohji Takara, Noriaki Tada, Eri Yoshikawa, Kazuhiro Yamamoto, Sayo Horibe, Toshiyuki Sakaeda, Kohshi Nishiguchi, Noriaki Ohnishi, Teruyoshi Yokoyama

    CANCER LETTERS   278 ( 1 )   88 - 96   2009.6

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    It is important to clarify the molecular characteristics of tumor cells showing multidrug resistance (MDR) and to identify the novel targets or biomarkers for chemotherapy. The aim of this study is to establish resistant HeLa sublines through exposure to SN-38, an active metabolite of irinotecan hydrochloride, and to investigate their molecular changes. HeLa cells were exposed to SN-38 at 1, 10, or 100 nM, and resistant clones were isolated and named HeLa/SN1, HeLa/SN10, and HeLa/SN100, respectively. Their cellular changes were examined based on growth inhibition assays, the function of ABCG2/BCRP, and a RT-PCR analysis of MDR-related protein. The sublines showed a decrease in sensitivity to not only SN-38 but also other chemotherapeutic agents as compared with HeLa cells. mRNA and protein levels of ABCG2/BCRP were increased, and the transport activity of ABCG2/BCRP was enhanced, in the resistant cells. In addition, the expression levels of ABCC1/MRP1, ABCC3/MRP3, and ABCC5/MRP5 were higher than in HeLa cells. The mRNA levels of GGTI encoding a gamma-glutamyl transferase, but not GCS encoding a gamma-glutamyl cysteine synthetase, were also higher. Other factors examined, i.e., topoisomerase, SLCO1B1, and apoptosis-regulating factors, were comparable among the cells. The overexpression of ABCG2/BCRP was involved in the mechanism of resistance in SN-38-tolerant cells, and ABCC1/MRP1, ABCC3/MRP3, ABCC5/MRP5, and GGT1 may also have participated. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

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  • Effects of nonsteroidal anti-inflammatory drugs on the expression and function of P-Glycoprotein/MDR1 in Caco-2 cells Reviewed

    Kohji Takara, Ryuhei Hayashi, Misato Kokufu, Kazuhiro Yamamoto, Noriaki Kitada, Noriaki Ohnishi, Teruyoshi Yokoyama

    DRUG AND CHEMICAL TOXICOLOGY   32 ( 4 )   332 - 337   2009

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    The aim of this study was to examine the effects of 16 kinds of nonsteroidal anti-inflammatory drugs (NSAIDs) on P-glycoprotein/MDR1 in Caco-2 cells as an intestinal epithelial cell model. Cells were treated with NSAIDs for 24 hours, and then, the expression of MDR1 mRNA was evaluated by reverse-transcriptase polymerase chain reaction. The function of MDR1 in cells pretreated with NSAIDs for 48 hours was evaluated by measuring the cellular amount of rhodamine123, which is a substrate of MDR1. The expression of MDR1 mRNA was increased by diclofenac, fenbufen, indomethacin, and nimesulide and the tended to be increased by meloxicam, mepirizole, and sulindac. However, pretreatment for 48 hours with diclofenac, indomethacin, or nimesulide, but not fenbufen, resulted in a significant increase in the amount of rhodamine123 accumulated. Although NSAIDs without effects on the expression of MDR1 mRNA altered the accumulation of rhodamine123 significantly, the efflux of rhodamine123 from cells was unchanged. In conclusion, the expression of MDR1 mRNA in Caco-2 cells was demonstrated to be increased by treatment with some NSAIDs, although the transport function of MDR1 was unchanged. These findings imply that the NSAIDs did not cause the drug interaction via MDR1 induction.

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Books

  • がん薬物療法時の腎障害診療ガイドライン2022

    日本腎臓学会, 日本癌治療学会, 日本臨床腫瘍学会, 日本腎臓病薬物療法学会( Role: Contributor)

    ライフサイエンス出版  2022.11  ( ISBN:9784897754574

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    Total pages:xxvi, 141p   Responsible for pages:10   Language:Japanese Book type:Scholarly book

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  • 腎臓病薬物療法トレーニングブック 第2版

    山本和宏( Role: Contributor ,  カルボプラチンの投与設計と腎機能評価)

    じほう  2019  ( ISBN:9784840752213

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  • 口から始める健康と美容

    谷口, 泰造, 仲野, 和彦, 山本, 和宏, 渡邉, 愛未, 英保, 武志, 久保, 茂正, 邵, 輝, 山田, 一夫 (1962)( Role: Contributor ,  第2章 口内炎の要因と口腔ケアについて)

    パブラボ,星雲社 (発売)  2016.2  ( ISBN:9784434215100

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  • JAID/JSC感染症治療ガイド2011

    山本和宏( Role: Joint editor)

    日本感染症学会・日本化学療法学会  2012.3 

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  • 東日本大震災において災害医療の中で経験したチーム医療 〜ボランティア活動の立場から〜

    山本和宏( Role: Contributor ,  東日本大震災 〜兵庫県のDMATと救護班等の活動報告〜)

    兵庫県災害医療センター  2012 

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  • Calvert式に用いる腎機能指標とカルボプラチンによる血液毒性発現の関連

    小林 理乃, 山本 和宏, 丹田 雅明, 糸原 光太郎, 北廣 優実, 大村 友博, 矢野 育子

    TDM研究   41 ( 2 )   158 - 158   2024.7

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  • 「がん薬物療法時の腎障害診療ガイドライン2022」について

    山本和宏

    日本薬剤師会雑誌   76 ( 2 )   2024

  • 血中濃度の変動要因を見極めよう 悩ましい薬物動態の諸問題 実践編-背景疾患のある患者のマネジメント 腎機能低下

    山本和宏

    月刊薬事   66 ( 3 )   2024

  • ニルマトレルビル/リトナビル併用時にタクロリムス濃度の異常高値を認めた腎移植症例

    冨田 猛, 木村 丈司, 山本 和宏, 宇田 篤史, 藤田 浩平, 荻原 孝史, 糸原 光太郎, 北廣 優実, 大村 友博, 矢野 育子

    日本医薬品情報学会総会・学術大会講演要旨集   25回   147 - 147   2023.6

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  • 高度腎機能低下患者におけるバンコマイシンAUC-guided TDMの安全性に関する検討

    藤田 浩平, 山本 和宏, 宇田 篤史, 荻原 孝史, 阪上 倫行, 田村 直暉, 木村 丈司, 糸原 光太郎, 北廣 優実, 大村 友博, 矢野 育子

    TDM研究   40 ( 2 )   176 - 176   2023.6

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  • がん薬物療法と薬物相互作用

    山本 和宏

    臨床薬理   54 ( 3 )   157 - 161   2023.5

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  • Search for compounds increasing the expression of ubiquitin ligase HRD1 and suppressing neuronal cell death

    西口大生, 大村友博, 佐登礼佳, 北廣優実, 山本和宏, 國正淳一, 矢野育子

    日本薬学会年会要旨集(Web)   143rd   2023

  • パーキンソン病発症に関連する小胞体ストレス関連分子SEL1Lを制御するmicroRNAの探索と血漿中microRNA発現量の検討

    西口大生, 大村友博, 大村友博, 野村月渚, 渡邉蘭, 北廣優実, 糸原光太郎, 山本和宏, 國正淳一, 松原和夫, 松原和夫, 矢野育子

    医療薬学フォーラム講演要旨集   31st   2023

  • 電解質異常 高カリウム血症 39 CKD患者における緊急性の高い高カリウム血症に対して治療薬は,何を選ぶ?

    山本和宏

    月刊薬事   65 ( 14 )   2023

  • 腎臓・泌尿器系疾患治療薬 CKD-MBD;慢性腎臓病に伴う骨ミネラル代謝異常 14 血清補正Ca濃度の高い高リン血症のCKD患者に対して薬剤は,何を選ぶ?

    山本和宏

    月刊薬事   65 ( 14 )   2023

  • 【がん薬物療法時の腎障害診療ガイドライン2022版のポイント】がん薬物療法開始前にみられる腎障害と腎機能の評価

    山本 和宏

    癌と化学療法   49 ( 11 )   1183 - 1187   2022.11

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    世界の死因の上位に悪性腫瘍や腎臓病が位置付けられ,それぞれの罹患者数も経年的に上昇している近年において,がんと腎臓病を併存する患者に薬物療法を適用する機会が増加している。がんと腎臓病の併存は,がん患者の腎障害発生と腎臓病患者や腎移植患者のがんの発生が想定されるが,それらの要因は多様であり対応も異なる。がん薬物療法の実施を検討する上で,開始時点の腎機能を適正に評価することや腎機能の低下する要因を明確に把握することは,治療の良好な予後につながる重要な過程である。また,がん患者では筋肉量が減少した患者の割合が高いことから,腎機能を評価する際は血清クレアチニン値に基づく糸球体濾過値の推算が過大評価となるリスクを理解しておく必要があり,実測値や各種推算値の特性を十分に理解した腎機能評価を行うことが重要である。なお,本解説は,日本腎臓学会・日本癌治療学会・日本臨床腫瘍学会・日本腎臓病薬物療法学会編『がん薬物療法時の腎障害診療ガイドライン2022』(ライフサイエンス出版)の第1章から抜粋し加筆したものである。(著者抄録)

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  • OncoNephrologyの現状と展望

    山本 和宏

    日本腎臓病薬物療法学会誌   11 ( 2 )   205 - 206   2022.8

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  • 【便秘と慢性腎臓病・透析医療】便秘を起こしやすい薬剤

    山本 和宏

    臨床透析   38 ( 4 )   367 - 371   2022.4

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    <文献概要>慢性腎臓病(CKD)や透析の患者は健常者と比較して便秘を起こしやすいことが知られており,薬物療法もその要因の一つである.CKD・透析患者において頻用されるポリマー型リン吸着薬やカリウム吸着薬は便秘を高頻度に発症させる.また,日本では高齢のCKD・透析患者も増加しており,高齢による潜在的な不適切処方により便秘を生じる可能性も高い.抗コリン作用,ヒスタミンおよびムスカリン受容体拮抗作用を有する薬剤は,便秘を生じる不適切処方の代表例である.本稿では,便秘を起こしやすい薬剤について,CKD・透析患者に投与される可能性が高いものを中心に高齢者への不適切処方例も含めて概説する.

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  • 【Onco-nephrology:悪性腫瘍治療と腎機能障害】CKD患者における抗がん薬治療 抗がん薬投与の際に注意すべき薬物相互作用

    山本 和宏

    腎と透析   92 ( 3 )   562 - 566   2022.3

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  • 症例に学ぶ腎機能低下患者さんの薬物適正使用 がん薬物療法時の最適な腎機能評価の重要性~カルボプラチン~

    山本和宏

    B.P. Up-to-Date   ( 129 )   2022

  • オンコネフロロジー がん患者における腎機能低下とがん免疫療法の最新知見

    山本 和宏

    日本腎臓病薬物療法学会誌   10 ( 特別号 )   S56 - S56   2021.10

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  • 【難しい数式も、TDMもわからない!「ニガテさん」のための薬物動態】(第5章)相互作用が見抜ける!遺伝子多型がわかる! 薬物代謝酵素・トランスポーターの遺伝子多型

    山本 和宏

    調剤と情報   27 ( 10 )   1802 - 1810   2021.7

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  • 【表在性皮膚真菌症 治療薬を活用するための基礎と実践総まとめ】患者背景を考慮した表在性皮膚真菌症治療・予防Q&A 腎機能低下・透析患者での経口抗真菌薬投与をどう考える? Invited

    山本 和宏

    薬局   71 ( 6 )   2549 - 2553   2020.5

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    <Key Points>◎表在性皮膚真菌症に使用される経口抗真菌薬は、いずれも肝代謝性で透析による除去も受けない。◎これらの薬剤は、原則、腎機能や透析による用量調整は不要であるが、末期腎不全患者においては血中濃度が上昇する報告もある。◎多くのCYPやトランスポーターは末期腎不全患者で発現量・活性が低下し、透析の実施により低下した発現量・活性が回復する。◎CYPの阻害と腎排泄の低下が同時に生じることにより血中濃度が顕著に上昇する併用薬には注意が必要である。◎CYP阻害作用を有する抗真菌薬の開始時は、検査値と合わせて処方全体を総合的に見直さなければならない。(著者抄録)

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  • 日本腎臓病薬物療法学会誌に投稿してみよう! 研究デザインから査読まで Invited

    辻本 雅之, 山本 武人, 山本 和宏, 川添 和義

    日本腎臓病薬物療法学会誌   8 ( 1 )   11 - 16   2019.4

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  • 【診療に活かす薬理・ブラッシュアップ】日常診療に直結する薬理学 治療薬物モニタリング(TDM) Invited

    阪上 倫行, 山本 和宏, 矢野 育子

    診断と治療   107 ( 2 )   173 - 179   2019.2

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    <Headline>1 治療薬物モニタリング(TDM)は血中濃度等の測定によって、今後の薬物治療に有益な判断をもたらす場合に目的を持って行う。2 分布容積とクリアランスに影響する変動因子を考慮しつつ、投与量と投与間隔を決定する。ただし、血中濃度を治療域に入れることのみを目的とせず、治療効果や副作用等のアウトカムを評価することが重要である。3 今後、血中濃度に加えて、治療効果の指標となるバイオマーカーやファーマコゲノミクス情報の活用や、採血量を低減させる技術や高感度な分析技術の利用がTDMの精密化に寄与する。(著者抄録)

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  • ゲノム医療の発展と薬剤師の役割 Invited

    Apo Talk   65   2 - 4   2019

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  • シグナル伝達因子に起因する間質性肺炎発症メカニズム

    山本 和宏, 中川 勉, 矢野 育子, 平井 みどり

    Medical Science Digest   44 ( 1 )   49 - 53   2018.1

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    分子標的治療の進展に伴い、間質性肺炎の報告が経年的に増加しているが、その詳細な発症メカニズムは解明されていない。線維化のin vitroモデルとなるEMTに関する研究が盛んに行われているが、近年、代表的因子であるサイトカインに依存しないシグナル伝達因子の活性変動によりEMTが亢進することが明らかとなり、分子標的治療薬に起因する間質性肺炎の発症メカニズムを考える上での重要な知見が得られている。本稿では、分子標的治療薬による間質性肺炎のシグナル伝達因子に起因する発症メカニズムについて概説する。(著者抄録)

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  • 薬剤師による処方設計 薬剤師主導のバンコマイシン処方設計に向けた取り組み

    住吉 霞美, 山本 和宏, 矢野 育子

    医薬ジャーナル   53 ( 10 )   2315 - 2319   2017.10

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    薬剤の投与設計における薬剤師の介入は,医薬品の適正使用の推進において非常に重要な職務である。神戸大学医学部附属病院(以下,当院)では,バンコマイシンの血中濃度測定が実施された全例に対し,薬剤部からの介入を行っている。特に初回投与設計については,当院のニーズに合わせた初回投与ノモグラムを過去のデータを基に作成し,業務の標準化を図っている。今後は,バンコマイシンの処方支援プロトコールに基づいた薬物治療管理の運用を目指している。本稿では,バンコマイシン治療における当院での取り組みを紹介し,薬剤師主導のバンコマイシンの治療計画について考えたい。(著者抄録)

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  • 薬剤師による処方設計(61)薬剤師主導のバンコマイシン処方設計に向けた取り組み

    住吉 霞美, 山本 和宏, 矢野 育子

    医薬ジャーナル   53 ( 10 )   131 - 135   2017.10

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  • 【研究・学会発表はじめの一歩】先輩が教える研究の始め方・取り組み方(File.3) 「やってみたい!」から始める研究活動

    山本 和宏

    薬事   59 ( 13特別付録 )   15 - 16   2017.10

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  • マルチキナーゼ阻害薬による皮膚障害におけるSTAT3の役割

    山本 和宏

    医療薬学   43 ( 5 )   237 - 244   2017.5

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    複数のキナーゼを阻害するマルチキナーゼ阻害薬(mTKI)は、手足皮膚反応(HFSR)とも呼ばれる皮膚障害を高頻度に発症することが治療上重要な問題となる。本稿では、mTKIによる皮膚障害の発症メカニズムにおけるsignal transducer and activator of transcription 3(STAT3)の役割と、発症のリスク因子の特定、ならびにメカニズムに基づく予防法の探索について概説した。ヒト表皮角化細胞に対するmTKIの増殖抑制作用は、STAT3の活性阻害を介したアポトーシス抑制因子の発現低下に起因する可能性が考えられる。また、PGE1はSTAT3の活性維持を介して、角化細胞に対するソラフェニブの増殖抑制作用を軽減し、それに伴う病理変化を軽減させることから、HFSRの新規予防薬となる可能性が示されている。

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  • シグナル伝達因子に起因する間質性肺炎発症メカニズム

    山本 和宏, 中川 勉, 矢野 育子, 平井 みどり

    別冊Bio Clinica: 慢性炎症と疾患   6 ( 1 )   121 - 125   2017.3

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    分子標的治療の進展に伴い、間質性肺炎の報告が経年的に増加しているが、その詳細な発症メカニズムは解明されていない。線維化のin vitroモデルとなるEMTに関する研究が盛んに行われているが、近年、代表的因子であるサイトカインに依存しないシグナル伝達因子の活性変動によりEMTが亢進することが明らかとなり、分子標的治療薬に起因する間質性肺炎の発症メカニズムを考える上での重要な知見が得られている。本稿では、分子標的治療薬による間質性肺炎のシグナル伝達因子に起因する発症メカニズムについて概説する。(著者抄録)

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  • 分子標的治療薬による皮膚障害のSTAT3を標的とした新規治療法の確立

    山本 和宏

    薬学研究の進歩   ( 33 )   115 - 119   2017.3

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  • 腎移植後耐糖能異常に影響する遺伝子多型

    横山直己, 小田晃廉, 小川悟史, 石村武志, 古川順也, 原田健一, 重村克巳, 日向信之, 中野雄造, 山本和宏, 平井みどり, 藤澤正人

    日本泌尿器科学会総会(Web)   105th   PP37 - 08   2017

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    J-GLOBAL

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  • メチルプレドニゾロンの吸収不良により造血細胞移植後急性移植片対宿主病のコントロールに難渋した小児急性リンパ性白血病の1症例

    田中 雄大, 山本 和宏, 大澤 史宜, 早川 晶, 山本 暢之, 森 健, 岡本 千明, 山下 和彦, 西岡 達也, 久米 学, 槇本 博雄, 平井 みどり

    TDM研究   33 ( 2 )   172 - 172   2016.5

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  • 個別化癌化学療法の実践のための口内炎発症マーカーの解析

    平野 剛, 山本 和宏, 大澤 史宜, 中川 勉, 平井 みどり

    医療の広場   56 ( 3 )   12 - 15   2016.3

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    癌化学療法に用いられる薬剤のうちメトトレキサートやフルオロウラシルなどの細胞障害性薬剤では副作用として口内炎があり、その発症機構として、薬剤の唾液分泌による口腔内の薬剤曝露により発症することが報告されている。薬物の唾液分泌にはP糖蛋白質が関与していることが報告されており、特にメトトレキサートやフルオロウラシルはP糖蛋白質の良好な基質とされている。P糖蛋白質をコードするMDR1遺伝子は日本人において遺伝子多型の存在が知られており、3435C&gt;Tと2677G&gt;A/Tの変異が薬物の唾液分泌に影響を及ぼすことが報告されている。今回著者等は、MDR1遺伝子多型の解析法と、唾液中メトトレキサート濃度のHPLCによる定量法を確立したので、その詳細を報告した。

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  • 21-6-O11-12 エベロリムスによる口内炎発症とMDR1遺伝子多型との関連性(薬物治療と遺伝子多型,口頭発表,一般演題,医療薬学の進歩と未来-次の四半世紀に向けて-)

    渡邉 愛未, 山本 和宏, 四宮 一昭, 平田 佐智, 石村 武志, 横山 直己, 三宅 秀明, 藤澤 正人, 中川 勉, 平野 剛, 平井 みどり

    日本医療薬学会年会講演要旨集   25   206 - 206   2015.10

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  • 21-5-O5-03 薬剤師によるSTOPP criteria version 2を用いたポリファーマシーへの介入(病棟薬剤業務,口頭発表,一般演題,医療薬学の進歩と未来-次の四半世紀に向けて-)

    木村 丈司, 小倉 史愛, 澤田 有記美, 宇田 篤史, 赤澤 由子, 野間 千尋, 野崎 晃, 山本 和宏, 五百蔵 武士, 西岡 達也, 久米 学, 槇本 博雄, 平井 みどり

    日本医療薬学会年会講演要旨集   25   200 - 200   2015.10

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  • 分子標的治療薬の皮膚障害における副作用マーカーのゲノム薬理学的解析

    山本 和宏, 三宅 秀明, 藤澤 正人, 尾藤 利憲, 錦織 千佳子, 平野 剛, 平井 みどり

    医療の広場   55 ( 7 )   27 - 29   2015.7

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    ソラフェニブ、スニチニブ、アキシチニブでの治療経験を有する腎細胞癌患者42例を対象に、分子標的治療薬による皮膚障害発症群(Grade 1以上)と非発症群に分類し、皮膚障害と皮膚の恒常性に関与する因子(Signal Transducer and Activator of Transcription(STAT)3)の遺伝子変異との関連性について検討した。その結果、皮膚障害の非発症群において、STAT3の遺伝子多型についてはG/G(野生型ホモ)の割合が有意に高かった。発症群においてはG/C(ヘテロ)、C/C(変異型ホモ)の割合が有意に高った。また、Grade 2以上の重症群とGrade 1以上の軽症群に分類し、STAT3遺伝子多型の分布を評価したところ、重症例でC/Cの割合が特に高かった。STAT3の発現量を低下させることで、分子標的治療薬の皮膚表皮角化細胞における増殖抑制作用が増強する可能性について、in vitroで検討を行った結果、si-RNAによりSTAT3をノックダウンさせた細胞はソラフェニブ細胞増殖抑制作用が顕著に高いことが示唆された。また、皮膚3次元モデルを用いて分子標的治療薬による細胞障害性、STAT3活性変動、角化亢進作用の評価を免疫染色法により評価したところ、Sorafenibを基底層側から曝露した皮膚3次元モデルは細胞の増殖が停止し、薄層化を認めた。また、角化層が剥離し、有棘層、顆粒層が表皮に剥出した。

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  • mTOR阻害薬による口内炎発症機構の分子生物学的解明と副作用バイオマーカーの探索

    山本 和宏

    今日の移植   27 ( 6 )   520 - 522   2014.12

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    mTOR阻害薬による口内炎発症機構の分子生物学的解明と副作用バイオマーカーについて検討した。ヒト頬粘膜上皮細胞(HO-1-N-1細胞)を用いた。サイトカインの定量はELISA法、蛋白質のリン酸化及び発現変動解析はウエスタンブロット法を用いた。唾液検体はエベロリムス内服中の腎移植患者を対象とした。エベロリムスによるIL-6の分泌亢進は、IL-6分泌を制御するp38と負に制御するErkの両方の活性化に起因する可能性が示唆された。エベロリムス内服中の腎移植患者5例における内服直前の唾液中エベロリムス濃度を測定し、1例のみ検出可能で1.1nMであった。

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  • 28-P2AM-035 携帯型心電計を用いたQT延長を誘発する薬剤使用患者に対しての病棟薬剤師の取り組み(職能拡大・スキルミックス,一般演題(ポスター),新時代を拓く医療薬学フロンティア)

    山岡 慶子, 大本 暢子, 山本 和宏, 西岡 達也, 久米 学, 槇本 博雄, 平野 剛, 平井 みどり

    日本医療薬学会年会講演要旨集   24   368 - 368   2014.8

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  • 27-O2PM-07 STAT3遺伝子多型と分子標的治療薬の皮膚障害発症頻度・重症度との関連性(がん薬物療法(副作用)2,優秀演題候補セッション4,新時代を拓く医療薬学フロンティア)

    山本 和宏, 平田 佐智, 山口 徹郎, 須野 学, 三宅 秀明, 藤澤 正人, 尾藤 利憲, 錦織 千佳子, 西岡 達也, 久米 学, 槇本 博雄, 中川 勉, 平野 剛, 平井 みどり

    日本医療薬学会年会講演要旨集   24   183 - 183   2014.8

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  • 土-P2-269 タクロリムス併用腎移植維持期におけるエベロリムス初期投与量の検討(TDM・投与設計,ポスター発表,一般演題,再興、再考、創ろう最高の医療の未来)

    山本 和宏, 田中 健太, 宇田 篤史, 久米 学, 槇本 博雄, 平野 剛, 平井 みどり

    日本医療薬学会年会講演要旨集   23   296 - 296   2013.8

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  • P2-274 ゾピクロン錠(アモバン錠^[○!R])とエスゾピクロン錠(ルネスタ錠^[○!R])の苦味評価(有害事象・副作用,ポスター,一般演題,岐路に立つ医療〜千年紀の目覚め〜よみがえれ!ニッポン!薬の改革は我らが手で!)

    宇田 篤史, 原口 珠実, 吉田 都, 向井 啓, 山本 和宏, 久米 学, 槇本 博雄, 平野 剛, 内田 享弘, 平井 みどり

    日本医療薬学会年会講演要旨集   22   424 - 424   2012.10

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  • 〈薬学教育6年制とこれからの展望〉次世代薬剤師を目指して

    山本和宏, 平野剛, 平井みどり

    医薬ジャーナル   48 ( 9 )   2149 - 2152   2012.9

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  • 薬学教育6年制とこれからの展望 次世代薬剤師を目指して

    山本 和宏, 平野 剛, 平井 みどり

    医薬ジャーナル   48 ( 9 )   63 - 66   2012.9

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    Other Link: http://search.jamas.or.jp/link/ui/2012368624

  • P-0881 腎移植後早期におけるタクロリムス徐放性製剤グラセプターの導入についての有用性の評価(一般演題 ポスター発表,TDM・投与設計,Enjoy Pharmacists' Lifestyles)

    山本 和宏, 冨田 猛, 山下 和彦, 宇田 篤史, 向井 啓, 久米 学, 槇本 博雄, 平野 剛, 平井 みどり

    日本医療薬学会年会講演要旨集   21   328 - 328   2011.9

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  • α遮断薬によるBCRP/ABCG2依存的な抗癌剤耐性の回復作用

    山本和宏, 高良恒史, 松原三佳, 吉川依里, 佐藤晃司, 辻紗矢香, 濱口良平, 辻本雅之, 北田徳昭, 栄田敏之, 横山照由

    日本薬学会年会要旨集   128th ( 4 )   221 - 221   2008.3

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Presentations

  • Calvert式に用いる腎機能指標とカルボプラチンによる血液毒性発現の関連

    小林 理乃, 山本 和宏, 丹田 雅明, 糸原 光太郎, 北廣 優実, 大村 友博, 矢野 育子

    TDM研究  2024.7  (一社)日本TDM学会

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    Event date: 2024.7

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  • 高度腎機能低下患者におけるバンコマイシンAUC-guided TDMの安全性に関する検討

    藤田 浩平, 山本 和宏, 宇田 篤史, 荻原 孝史, 阪上 倫行, 田村 直暉, 木村 丈司, 糸原 光太郎, 北廣 優実, 大村 友博, 矢野 育子

    TDM研究  2023.6  (一社)日本TDM学会

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    Event date: 2023.6

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  • ニルマトレルビル/リトナビル併用時にタクロリムス濃度の異常高値を認めた腎移植症例

    冨田 猛, 木村 丈司, 山本 和宏, 宇田 篤史, 藤田 浩平, 荻原 孝史, 糸原 光太郎, 北廣 優実, 大村 友博, 矢野 育子

    日本医薬品情報学会総会・学術大会講演要旨集  2023.6  (一社)日本医薬品情報学会

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    Event date: 2023.6

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  • 粘度可変型流動食マーメッド®と胃酸分泌抑制薬の併用による下痢発現のリスクに関する検討

    平島七海, 森尾佳代子, 住吉霞美, 山本和宏, 大村友博, 矢野育子

    第10回日本薬剤師レジデントフォーラム  2021.3.14  日本薬剤師レジデント制度研究会

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    Event date: 2021.3.14

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    Venue:WEB開催  

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  • 院外処方箋への臨床検査値印字が保険薬局の処方介入に与える影響

    益成宏美, 冨田猛, 木村丈司, 髙木妙子, 野﨑晃, 山本和宏, 大村友博, 坂根稔康, 國正淳一, 宮田興子, 矢野育子

    第10回日本薬剤師レジデントフォーラム  2021.3.14  日本薬剤師レジデント制度研究会

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    Event date: 2021.3.14

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  • 若年の腎機能正常患者におけるVCM有効血中濃度への到達に影響する因子の調査

    岡誠吾, 阪上倫行, 山本和宏, 大村友博, 坂根稔康, 國正淳一, 宮田興子, 矢野育子

    第10回日本薬剤師レジデントフォーラム  2021.3.14  日本薬剤師レジデント制度研究会

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  • 薬剤師によるTDM関連オーダリング補助業務の有用性の検討

    村川亜光, 山本和宏, 石井順子, 阪上倫行, 高木妙子, 清水倫子, 大村友博, 坂根稔康, 國正淳一, 宮田興子, 矢野育子

    第10回日本薬剤師レジデントフォーラム  2021.3.14  日本薬剤師レジデント制度研究会

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  • 病院 - 保険薬局間のシームレスな吸入指導体制の構築に向けたツールの作成とその評価

    高橋慶, 清水倫子, 大本暢子, 山本和宏, 大村友博, 矢野育子

    第10回日本薬剤師レジデントフォーラム  2021.3.14  日本薬剤師レジデント制度研究会

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  • 一包化錠剤仕分け装置TABSORT®の効率的かつ安全性の高い運用方法の検討

    藤澤諒子, 山下和彦, 岡崎裕太朗, 山本和宏, 大村友博, 矢野育子

    第10回日本薬剤師レジデントフォーラム  2021.3.14  日本薬剤師レジデント制度研究会

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  • 進行固形がん患者を対象とした心血管疾患予防のための降圧薬の使用実態に関する調査

    丹田雅明, 塩見真由, 山本和宏, 國正淳一, 槇本博雄, 大村友博, 矢野育子

    第42回日本病院薬剤師会近畿学術大会  2021.1.30 

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  • よくわかる腎機能低下患者の抗がん薬個別化投与設計

    山本和宏

    第14回日本腎臓病薬物療法学会学術集会  2020.12.14 

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • Reinforced collaboration between community pharmacies and hospital for the management of oral anti-cancer therapy using information sharing tools and team-based learning

    Ueda R, Tanda M, Ito T, Enomoto A, Iida M, Mizuta N, Yamamoto K, Makimoto H, Omura T, Yano I

    2020.10.24 

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  • 病棟薬剤師に対する手指衛生の教育効果と評価者としての薬学部実務実習生への波及効果

    柴田京香, 飯田真之, 宇田篤史, 出田理恵, 八幡眞理子, 大本暢子, 山本和宏, 大村友博, 矢野育子

    第30回日本医療薬学会年会  2020.10.24  日本医療薬学会

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    Event date: 2020.10.24 - 2020.11.1

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  • 人工弁置換術後のワルファリン導入下におけるPT-INR値に関する解析

    森岡朝美, 清水倫子, 山本和宏, 大村友博, 井上武, 岡田健次, 矢野育子

    第30回日本医療薬学会年会  2020.10.24 

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  • レンバチニブによる有害事象の発生予測に対するALBI Gradeの有用性の検討

    松本由季, 榎本大智, 山本和宏, 大村友博, 小松昇平, 矢野嘉彦, 矢野育子

    第30回日本医療薬学会年会  2020.10.24 

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  • 薬剤師による抗菌薬血中濃度測定オーダー登録と注射薬仮登録がもたらす実践的有用性の評価

    村川亜光, 山本和宏, 石井順子, 阪上倫行, 清水倫子, 槇本博雄, 大村友博, 坂根稔康, 國正淳一, 宮田興子, 矢野育子

    第30回日本医療薬学会年会  2020.10.24 

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  • 全病棟を対象としたボリファーマシー対策の実践

    飯田真之, 木村丈司, 松本久美子, 栗村朋子, 山本和宏, 矢野育子

    第4回日本老年薬学会学術大会  2020.6.28  日本老年薬学会

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  • PETINIA法による血中ミコフェノール酸測定試薬の基準測定法LC-MS/MS法との比較

    大籔 智奈美, 佐藤 伊都子, 山本 和宏, 中町 祐司, 三枝 淳

    臨床化学  2018.7  (一社)日本臨床化学会

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    Event date: 2018.7

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  • メチルプレドニゾロンの吸収不良により造血細胞移植後急性移植片対宿主病のコントロールに難渋した小児急性リンパ性白血病の1症例

    田中 雄大, 山本 和宏, 大澤 史宜, 早川 晶, 山本 暢之, 森 健, 岡本 千明, 山下 和彦, 西岡 達也, 久米 学, 槇本 博雄, 平井 みどり

    TDM研究  2016.5  (一社)日本TDM学会

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  • Association of single nucleotide polymorphisms (SNP) in STAT3 gene with hand-foot skin reaction in metastatic renal cell carcinoma patients treated with multi-kinase inhibitor.

    Kazuhiro Yamamoto, Takeshi Ioroi, Kazuaki Shinomiya, Sachi Hirata, Kenichi Harada, Manabu Suno, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Toshinori Bito, Chikako Nishigori, Hideaki Miyake, Masato Fujisawa, Midori Hirai

    JOURNAL OF CLINICAL ONCOLOGY  2015.5  AMER SOC CLINICAL ONCOLOGY

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  • エルロチニブによるざ瘡様皮疹モデルの確立と分子機構の解明

    久土智也, 久土智也, 山本和宏, 中川勉, 尾藤利憲, 錦織千佳子, 濱口常男, 平野剛, 平井みどり

    日本薬学会年会要旨集(CD-ROM)  2015 

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    Language:Japanese  

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  • 消化管上皮細胞モデルにおけるABCB1発現・機能に及ぼすエベロリムス長期曝露の影響

    中山優子, 高良恒史, 山本和宏, 大村友博, 矢野育子

    日本薬学会第141年会  2021.3.29 

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    Venue:WEB開催  

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  • セルトラリンに起因するセロトニン症候群関連症状のリスク因子の探索

    山本和宏, 松山夏実, 國正淳一, 大村友博, 矢野育子

    日本薬学会第141年会  2021.3.27 

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  • セロトニン受容体拮抗型制吐薬投与患者における便秘発現の実態調査

    津田瑞季, 伊藤雄大, 丹田雅明, 山本和宏, 大村友博, 坂根稔康, 國正淳一, 宮田興子, 矢野育子

    第10回日本薬剤師レジデントフォーラム  2021.3.14  日本薬剤師レジデント制度研究会

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    Venue:WEB開催  

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  • 病院と保険薬局の連携強化を目的とした研修会(Team Based Learning)による人材育成

    植田梨沙, 丹田雅明, 伊藤雄大, 榎本彩花, 飯田真之, 水田直美, 山本和宏, 槇本博雄, 大村友博, 矢野育子

    日本臨床腫瘍薬学会学術大会2021  2021.3.6 

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  • 抗がん薬調製ロボット導入前後における抗がん薬関連業務の比較

    伊藤雄大, 丹田雅明, 水田直美, 丸上奈穂, 山口由加里, 植田梨沙, 山本和宏, 槇本博雄, 大村友博, 矢野育子

    第27 回日本がんチーム医療研究会  2021.2.13 

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  • Impact of sunitinib on the expression of cornifying factors in human epidermal 3D skin models International conference

    Yoshida A, Yamamoto K, Ishida T, Omura T, Itoh T, Nishigori C, Sakane T, Yano I

    The 4th International Cancer Research Symposium of Training Plan for Oncology Professionals  2021.2 

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  • 抗がん薬のゲノム薬理とがんゲノム医療

    山本和宏

    令和2年度 熊本大学・薬学教育部特論講義  2021.1.15 

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  • 腎細胞癌患者を対象とした2週投与1週休薬スケジュール下におけるスニチニブ至適血中濃度に関する検討

    伊藤雄大, 山本和宏, 北村匠, 古川順也, 原田健一, 藤澤正人, 大村友博, 矢野育子

    第41回日本臨床薬理学会学術総会  2020.12.3 

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  • 薬剤師が知っておきたいゲノムと薬のはなし

    山本和宏

    千葉病院薬剤師会スキルアップセミナー  2020.10.23 

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  • 慢性腎臓病患者の薬物治療適正化に向けた病診薬連携

    山本和宏

    第63回日本腎臓学会学術総会  2020.8.20 

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  • ポリファーマシーに対する薬剤師介入の取り組み

    大村友博, 木村丈司, 山本和宏, 矢野育子

    日本病院薬剤師会 東北ブロック第10回学術大会  2020.6.30 

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  • 腎移植後にスニチニブ治療を開始した腎癌患者におけるタクロリムス・エベロリムスの薬物動態モデル解析

    2020.3.20 

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  • Physiologically-based pharmacokinetic modeling and simulation of serum risperidone and paliperidone concentrations in pregnant woman taking risperidone and in her baby

    2020.3 

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  • がん悪液質に対する補中益気湯による改善効果に関する調査

    2020.3 

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  • 神戸大学・神戸薬科大学薬剤師レジデントにおける教育関連業務

    2020.3 

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  • レンバチニブによる有害事象の発生予測に対するALBIスコアの有用性の検討

    2020.3 

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  • 薬剤師によるTDMオーダーと注射仮登録の有用性評価

    2020.3 

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  • 人工弁置換術後のワルファリン導入におけるプロトロンビン時間国際標準比推移の現状と課題

    2020.3 

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  • 生下時より経時的に薬物血中濃度を測定し得たリスペリドン内服母体児の1例

    2020.3 

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  • スニチニブによる表皮角化細胞のkeratin 6AおよびSERPINB1発現変動

    2020.3 

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  • 分子標的型抗がん薬の副作用に関する基礎・臨床の統合的研究

    2020.2 

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  • 経口分子標的型抗がん薬のTDM

    2020.2 

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  • 乳児におけるテイコプラニン血中濃度の評価

    2020.2 

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  • 抗がん薬混合調製ロボットの導入と稼働状況

    2020.2 

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  • がん薬物療法における薬理遺伝学の実際

    2020.2 

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  • Monitoring of concentrations of sunitinib, tacrolimus, and everolimus in the patient with metastatic renal cell carcinoma after renal transplantation International conference

    2020.2 

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  • 薬剤師主導型臨床研究へのアプローチ

    2020.2 

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  • 新生児の先天性サイトメガロウイルス感染症患者におけるガンシクロビル血中濃度測定と生理学的薬物動態モデルを用いたシミュレーション

    2019.12 

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  • Population pharmacokinetic modeling of everolimus in renal transplant patients with multiple immunosuppressive therapy.

    2019.12 

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  • Role of STAT3 in hand–foot skin reaction induced by multi-targeted tyrosine kinase inhibitors

    2019.12 

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  • 臨床検査値に基づく疑義照会の実践

    2019.12 

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  • 学会誌編集委員会セミナー:研究のデザインと進め方 ~研究の筋書き~

    2019.11 

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  • スキルアップセミナー:適正な腎機能評価に基づく抗がん薬投与設計入門講座

    2019.11 

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  • 神戸大学医学部附属病院における実務実習

    2019.11 

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  • 最新のPGx研究: STAT3遺伝子多型と分子標的型抗がん薬の副作用

    2019.11 

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  • プロトンポンプ阻害薬の院内フォーミュラリー策定による後発医薬品の使用促進と薬剤費の削減効果

    2019.11 

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  • プロトコルおよび 薬剤部門システムを活用した DOACの薬物相互作用マネジメント

    2019.11 

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  • 医薬品不適切使用症例検出システムの構築

    2019.11 

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  • 腎機能低下時の薬物療法について

    2019.11 

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  • 病診薬連携による薬物治療適正化〜薬剤師の立場から〜

    2019.10 

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  • SGLT2阻害剤の皮膚障害に関する研究―ラット体内動態データの薬物動態学的解析とマイクロアレイ解析―

    2019.10 

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  • がんゲノム医療における薬剤師の役割

    2019.9 

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  • PHARMACOKINETIC ASSESSMENT FOR A CASE OF ALPRAZOLAM-INDUCED NEONATAL ABSTINENCE SYNDROME USING PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL International conference

    2019.9 

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  • 肺由来細胞のエベロリムス反応性におけるSTAT3遺伝子多型の影響

    2019.7 

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  • 血清クレアチニン低値の患者におけるバンコマイシン母集団薬物動態解析

    2019.7 

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  • ICU入室患者における睡眠薬使用後のせん妄発現に対するリスク因子の探索

    2019.7 

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  • 処方オーダリングシステムにおける検査値に対応した処方禁忌チェック機能の導入と評価

    2019.6 

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  • ラモトリギンTDMの現状と血中濃度の変動因子に関する調査

    2019.5 

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  • チーム基盤型学習を用いた経口抗がん薬に関する勉強会の有用性の検討

    植田梨沙, 伊藤雄大, 丹田雅明, 飯田真之, 山本和宏, 槇本博雄, 矢野育子

    日本臨床腫瘍薬学会学術大会2019  2019.3.24 

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  • 経口抗がん薬を含む術後補助化学療法における病院および保険薬局薬剤師との協働支援の有用性評価

    榎本彩花, 丹田雅明, 植田梨沙, 水田直美, 山本和宏, 西岡達也, 槇本博雄, 坂根稔康, 國正淳一, 濵口常男, 北河修治, 矢野育子

    日本臨床腫瘍薬学会学術大会2019  2019.3.24 

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  • 新規Bcl-2選択的阻害剤の長期間曝露がヒト白血病細胞株に及ぼす影響

    中山優子, 高良恒史, 峯垣哲也, 山本和宏, 矢野育子

    日本薬学会第139年会  2019.3.22 

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  • 化学療法誘発性の悪心・嘔吐予防目的のオランザピン投与量に関する検討

    穐原裕奈, 山本和宏, 水田直美, 丹田雅明, 伊藤雄大, 坂根稔康, 國正淳一, 濵口常男, 北河修治, 矢野育子

    日本薬学会第139年会  2019.3.22 

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  • Molecular characteristics of human leukemia cell line after the long-term exposure to the Bcl-2 inhibitor ABT-199 International conference

    Yuko Nakayama, Kohji Takara, Tetsuya Minegaki, Kazuhiro Yamamoto, Ikuko Yano

    The 2nd International Cancer Research Symposium of Training Plan for Oncology Professionals  2019.2.3 

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  • 改訂薬学教育モデルコア・カリキュラムに準拠した病院実務実習のプログラムの作成と評価

    山本和宏, 藤田浩平, 秋山恵里, 清水倫子, 久保萌子, 松本久美子, 谷藤亜希子, 大本暢子, 矢野育子

    第40回日本病院薬剤師会近畿学術大会  2019.1.20 

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  • 検査値連動型の処方チェックシステムを用いた疑義照会の有用性 Invited

    冨田猛, 山本和宏, 野﨑晃, 高橋知子, 木村丈司, 西岡達也, 久米学, 槇本博雄, 矢野育子

    平成30年度大学病院情報マネジメント部門連絡会議  2019.1 

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  • がん領域で生かす腎についての考え方

    山本和宏

    第28回日本医療薬学会年会  2018.11.25 

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  • ポリファーマシーの効率的な検出と保険薬局との連携を目指したwebシステムの構築

    野崎晃, 山本和宏, 木村丈司, 松田美玖, 高橋知子, 小倉史愛, 矢野育子

    第28回日本医療薬学会年会  2018.11.24 

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  • 個別化医療のいまとこれからを考える 〜がんゲノム医療からプライマリ・ケアまで〜:趣旨説明

    山本和宏

    第28回日本医療薬学会年会  2018.11.24 

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  • ポリファーマシー対策のための医薬連携合同勉強会の開催とアンケートによる現状調査

    秋山恵里, 木村丈司, 山本和宏, 飯田真之, 藤田弥佐, 清水倫子, 久保萌子, 住吉霞美, 番匠咲帆, 三島唯, 戸田飛鳥, 矢野育子

    第28回日本医療薬学会年会  2018.11.23 

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  • 研究のデザインと進め方 〜研究の筋書き〜

    山本和宏

    第12回日本腎臓病薬物療法学会学術集会・総会  2018.10.20 

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  • Investigation of activity guidelines of disaster hospitals through disaster activities in the Ishinomaki medical zone during the Great East Japan Earthquake International conference

    Yuji Maeda, Yoshihiro Ando, Yoshiro Nishimura, Ikuko Yoshitugu, Makiko Kai, Aska Toda, Kazuhiro Yamamoto, Takashi Okunaga, Minoru Konishi, Shinichi Nakayama, Tadashi Ishii

    The 14th Asia Pacific Conference on Disaster Medicine  2018.10.16 

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  • Influence of CYP2C19 and CYP3A5 polymorphisms on tacrolimus pharmacokinetics in the combination therapy with lansoprazole in Japanese renal transplant recipients International conference

    Kazuhiro Yamamoto, Masashi Iida, Ayaka Yoshida, Takahiro Ito, Naoki Yokoyama, Takeshi Ishimura, Masato Fujisawa, Ikuko Yano

    The 16th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology  2018.9.18 

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  • PETINIA法による血中ミコフェノール酸測定試薬の基準測定法LC-MS/MS法との比較

    大籔智奈美, 佐藤伊都子, 山本和宏, 中町祐司, 三枝淳

    第58回日本臨床化学会年次学術集会  2018.8 

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  • リスペリドンによる錐体外路症状とCYP2D6遺伝子多型の関連

    伊藤雄大, 山本和宏, 大澤史宜, 大塚郁夫, 菱本明豊, 曽良一郎, 平井みどり, 矢野育子

    日本医療薬学会 第2回フレッシャーズ・カンファランズ  2018.7.8 

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  • Effects of sunitinib on the expression of keratin 9 in human keratinocyte cell lines and a 3D skin model International conference

    Ayaka Yoshida, Kazuhiro Yamamoto, Akane Murakawa, Takahiro Ishida, Tsutomu Nakagawa, Tomoo Itoh, Ikuko Yano

    18th World Congress of Basic and Clinical Pharmacology  2018.7.5 

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  • ケラチン9の発現に及ぼす皮膚高次構造とスニチニブの影響

    村川亜光, 山本和宏, 吉田彩夏, 濵口常男, 中川勉, 矢野育子

    医療薬学フォーラム2018 第26回 クリニカルファーマシーシンポジウム  2018.6.24 

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  • エベロリムス長期曝露肺胞上皮細胞の上皮間葉転換に寄与するケモカインの探索

    岩間弓奈, 山本和宏, 濵口常男, 中川勉, 矢野育子

    医療薬学フォーラム2018 第26回 クリニカルファーマシーシンポジウム  2018.6.23 

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  • アルプラゾラム服用妊婦から出生した児の薬物血中濃度測定を行った一症例

    三島唯, 山本和宏, 橋本真梨, 福嶋祥代, 藤岡一路, 矢野育子

    第35回日本TDM学会  2018.5.26 

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  • 抗癌剤耐性細胞におけるアミノ酸トランスポーターの発現解析

    中山優子, 大西晃, 山本成人, 峯垣哲也, 山本和宏, 高良恒史

    日本薬学会第138年会  2018.3.28 

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  • がん分子標的治療による副作用の分子メカニズムの解明と克服法の確立に向けた病院薬剤師の挑戦

    山本和宏

    日本薬学会第138年会  2018.3.28 

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  • 持参薬確認業務における危険予知トレーニングツールの開発とその評価

    谷藤亜希子, 山本和宏, 木村丈司, 五百蔵武士, 西岡達也, 久米学, 槇本博雄, 矢野育子

    日本薬学会第138年会  2018.3.27 

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  • nab-Paclitaxelと併用薬混合時の安定性に関する検討

    水田直美, 中川勉, 山本和宏, 西岡達也, 久米学, 槇本博雄, 矢野育子, 南博信, 平井みどり

    臨床腫瘍薬学会学術大会2018  2018.3.18 

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  • ヒトケラチノサイト由来細胞株におけるSGLT2阻害剤による細胞障害性の比較

    松本彩夏, 辻本雅之, 折方琴音, 白土恵理, 辻本美菜, 峯垣哲也, 河渕真治, 伊藤由佳子, 栄田敏之, 山本和宏, 錦織千佳子, 西口工司

    第27回日本医療薬学会年会  2017.11.5 

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  • 統合失調症患者における錐体外路症状発現に及ぼすCYP2D6遺伝子多型の影響

    伊藤雄大, 山本和宏, 西岡達也, 久米学, 槇本博雄, 大塚郁夫, 菱本明豊, 曽良一郎, 平井みどり, 矢野育子

    第27回日本医療薬学会年会  2017.11.4 

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  • 検査値連動型の処方チェックシステムを用いた疑義照会の有用性

    冨田猛, 山本和宏, 野崎晃, 宇田篤史, 阪上倫行, 西岡達也, 久米学, 槇本博雄, 平井みどり, 矢野育子

    第27回日本医療薬学会年会  2017.11.4 

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  • 味覚センサを用いたゾピクロン錠の飲料による苦味マスキング効果およびメカニズムの検討

    吉田都, 宇田篤史, 原口珠実, 小島穂菜美, 山本和宏, 平井みどり, 内田享弘

    第27回日本医療薬学会年会  2017.11.3 

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  • ゲノム情報活用支援システムの有用性の評価と課題

    山本和宏

    第27回日本医療薬学会年会  2017.11.3 

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  • Impact of STAT3 genetic polymorphism on sunitinib-induced stomatitis in Japanese renal cell carcinoma patients International conference

    Aimi Watanabe, Kazuhiro Yamamoto, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Hideaki Miyake, Masato Fujisawa, Tsutomu Nakagawa, Ikuko Yano, Midori Hirai

    The 15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology  2017.9.27 

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  • Bench-to-bedside research for the dermatological side effects induced by multiple tyrosine kinase inhibitors Invited International conference

    2017.9.27 

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    Language:English   Presentation type:Symposium, workshop panel (nominated)  

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  • Molecular cornifying mechanisms of multi-targeted tyrosine kinase inhibitors-induced hand-foot skin reaction based on genetic differences of STAT3

    Kazuhiro Yamamoto, Takahiro Ishida, Tsutomu Nakagawa, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Hideaki Miyake, Masato Fujisawa, Chikako Nishigori, Ikuko Yano, Midori Hirai

    The 15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology  2017.9.27 

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  • 腎移植患者における術後早期のタクロリムス血中濃度の評価

    飯田真之, 山本和宏, 伊藤雄大, 大澤史宜, 西岡達也, 久米学, 槇本博雄, 横山直己, 石村武志, 藤澤正人, 矢野育子

    第34回日本TDM学会・学術大会  2017.9.23 

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  • 分子標的治療薬の有効性・副作用とSTAT3遺伝子多型の関連

    山本和宏

    第15回日本臨床腫瘍学会学術集会  2017.7.29 

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  • 分子標的治療薬の適正使用に向けた遺伝子多型解析の実践 Invited

    山本和宏

    第11回日本緩和医療薬学会年会  2017.6.4 

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  • ChREBPのグルコース濃度依存的なDNA結合はO-GlcNAc修飾により制御される

    中川勉, 吉村友希, 崎山晴彦, 中川孝俊, 山本和宏, 矢野育子, 藤原範子, 朝日通雄, 鈴木敬一郎, 平井みどり

    第64回日本生化学会近畿支部例会  2017.5.27 

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  • 腎移植後耐糖能異常に影響する遺伝子多型

    横山直己, 石村武志, 小田晃廉, 小川悟史, 古川順也, 原田健一, 重村克巳, 日向信之, 山本和宏, 平井みどり, 藤澤正人

    第105回日本泌尿器科学会総会  2017.4.22 

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  • 学会発表の次のステップ~エビデンスとして残すために~ Invited

    山本和宏

    第 1 回 医療薬学教育セミナー  2017.4.16 

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  • Association of Single Nucleotide Polymorphisms in STAT3, ABCB1, and ABCG2 with Stomatitis in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib: A Retrospective Analysis in Japanese Patients International conference

    Aimi Watanabe, Kazuhiro Yamamoto, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Hideaki Miyake, Masato Fujisawa, Tsutomu Nakagawa, Ikuko Yano, Midori Hirai

    The 5th International Symposium of Training Plan for Oncology Professionals  2017.3.10 

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Industrial property rights

  • 薬剤性間質性肺炎の易発症性判定用マーカーを用いた薬剤性間質性肺炎の易発症性を判定する方法およびキット

    山本 和宏, 平井 みどり

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    Applicant:国立大学法人神戸大学

    Application no:特願2015-147366  Date applied:2015.7.27

    Announcement no:特開2017-023090  Date announced:2017.2.2

    J-GLOBAL

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  • 薬剤性間質性肺炎の易発症性判定用マーカーを用いた薬剤性間質性肺炎の易発症性を判定する方法およびキット

    山本和宏, 平井みどり

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    Application no:特願2015-147366 

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  • 疎水性物質包接剤およびそれを用いた疎水性物質の可溶化方法

    谷口泰造, 宮本和英, 炬口真理子, 角山圭一, 福田勝, 鈴木利雄, 甲元一也, 山本和宏, 渡邊愛未

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    Application no:特願2014-251325 

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Awards

  • 学術奨励賞

    2024.12   臨床薬理研究振興財団   腎機能障害患者におけるがん薬物療法の新規用量設計法の確立に向けた生理学的薬物動態モデル&シミュレーションとビッグデータの統合解析

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  • JPHCS誌論文賞

    2024.6   日本医療薬学会   Significance of pharmacist intervention to oral antithrombotic therapy in the pharmaceutical outpatient clinic of cardiovascular internal medicine: a retrospective cohort study

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  • 第6回フレッシャーズ・カンファランス優秀演題発表賞

    2023.6   日本医療薬学会   肺胞上皮細胞におけるエベロリムスの上皮間葉転換誘導とシグナル伝達因子の関連

    高橋大, 山本和宏, 西口大生, 糸原光太郎, 北廣優実, 大村友博, 國正淳一, 矢野育子

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  • 第16回日本緩和医療薬学会年会口頭発表最優秀演題賞受賞

    2023.5   日本緩和医療薬学会   非がん性疼痛に対して使用されるオピオイド性鎮痛薬の薬剤師による使用状況モニタリングとその効果

    飯田真之,志田有里,番匠咲帆,大本暢子,山下和彦,槇本博雄,山本和宏,大村友博,矢野育子

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  • 日本臨床腫瘍薬学会学術大会2023最優秀演題賞

    2023.3   日本臨床腫瘍薬学会   免疫チェックポイント阻害薬投与患者の好中球リンパ球比による層別化とプロトンポンプ阻害薬の併用による生命予後への影響

    堀智貴, 山本和宏, 伊藤武文, 生島繁樹, 大村友博, 矢野育子

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  • 日本薬学会第143会年会学生優秀発表賞

    2023.3   日本薬学会   ユビキチンリガーゼHRD1を誘導する化合物の探索と神経細胞死抑制効果の検討

    西口大生,大村友博,佐登礼佳,北廣優実,山本和宏,國正淳一,矢野育子

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  • 2022年度日本薬学会関西支部奨励賞

    2022.12   日本薬学会関西支部   分子標的型抗がん薬による間質性肺疾患発症の分子機構に基づく予測法の開発

    山本和宏

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  • JPHCS誌論文賞

    2022.6   日本医療薬学会   Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan

    Jumpei Saito, Naomi Nadatani, Makoto Setoguchi, Masahiko Nakao, Hitomi Kimura, Mayuri Sameshima, Keiko Kobayashi, Hiroaki Matsumoto, Naoki Yoshikawa, Toshihiro Yokoyama, Hitomi Takahashi, Mei Suenaga, Ran Watanabe, Kinuko Imai, Mami Obara, Mari Hashimoto, Kazuhiro Yamamoto, Naoko Fujiwara, Wakako Sakata, Hiroaki Nagai, Takeshi Enokihara, Sayaka Katayama, Yuta Takahashi, Mariko Araki, Kanako Iino, Naoko Akiyama, Hiroki Katsu, Kumiko Fushimi, Tomoya Takeda, Mayumi Torimoto, Rina Kishi, Naoki Mitsuya, Rie Kihara, Yuki Hasegawa, Yukihiro Hamada, Toshimi Kimura, Masaki Wada, Ayano Tanzawa, Akimasa Yamatani

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  • 第10回江口記念がん優秀論文賞

    2022.6   日本病院薬剤師会   Safety and Efficacy of Bis-Glyceryl Ascorbate as Prophylaxis for Hand-Foot Skin Reaction: A Single-Arm, Open-Label Phase I/II Study (DGA Study)

    Kazuhiro Yamamoto, Satoshi Nishiyama, Makoto Kunisada, Masashi Iida, Takahiro Ito, Takeshi Ioroi, Hiroo Makimoto, Tomohiro Omura, Kenichi Harada, Masato Fujisawa, Chikako Nishigori, Ikuko Yano

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  • 第27回日本がんチーム医療研究会優秀演題賞

    2021.2   日本がんチーム医療研究会   抗がん薬調製ロボット導入前後における抗がん薬関連業務の比較

    伊藤雄大, 丹田雅明, 水田直美, 丸上奈穂, 山口由加里, 植田梨沙, 山本和宏, 槇本博雄, 大村友博, 矢野育子

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  • 第40回日本臨床薬理学会学術総会優秀演題賞(ポスター発表)

    2019.12   日本臨床薬理学会   新生児の先天性サイトメガロウイルス感染症患者におけるガンシクロビル血中濃度測定と生理学的薬物動態モデルを用いたシミュレーション

    山本和宏, 大山正平, 福嶋祥代, 橋本真梨, 山川恵, 藤原尚子, 藤岡一路, 飯島一誠, 大村友博, 矢野育子

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  • 「IATDMCT学術大会」派遣賞

    2019.5   日本TDM学会   PHARMACOKINETIC ASSESSMENT FOR A CASE OF ALPRAZOLAM-INDUCED NEONATAL ABSTINENCE SYNDROME USING PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL

    Kazuhiro Yamamoto, Sachiyo Fukushima, Yui Mishima, Mari Hashimoto, Kei Yamakawa, Kazumichi Fujioka, Kazumoto Iijima, Ikuko Yano

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  • 論文賞

    2017.11   日本医療薬学会   STOPP Criteriaを用いた高齢者のポリファーマシーに対する薬剤師による介入

    小倉史愛, 木村丈司, 宇田篤史, 戸田飛鳥, 赤澤由子, 山本和宏, 五百蔵武士, 西岡達也, 久米学, 槇本博雄, 平井みどり

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    Award type:Award from Japanese society, conference, symposium, etc. 

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  • Ebihara Prize

    2017   Molecular cornifying mechanisms of multi-targeted tyrosine kinase inhibitors-induced hand-foot skin reaction based on genetic differences of STAT3

    Kazuhiro Yamamoto

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  • 奨励賞

    2016   日本医療薬学会   腎細胞がんに対する分子標的治療薬の有効性・副作用予測因子に関する研究

    山本和宏

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  • 優秀演題賞(共著)

    2015   第25回日本医療薬学会年会   薬剤師によるSTOPP criteria version 2を用いたポリファーマシーへの介入

    木村丈司, 小倉史愛, 澤田有記美, 宇田篤史, 赤澤由子, 野間千尋, 野崎晃, 山本和宏, 五百蔵武士, 西岡達也, 久米学, 槇本博雄, 平井みどり

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  • 優秀演題賞

    2014   第24回日本医療薬学会年会   STAT3遺伝子多型と分子標的治療薬の皮膚障害発症頻度・重症度との関連性

    山本和宏, 平田佐智, 山口徹郎, 須野学, 三宅秀明, 藤澤正人, 尾藤利憲, 錦織千佳子, 西岡達也, 槇本博雄, 久米学, 中川勉, 平野剛, 平井みどり

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  • 優秀発表賞(共著)

    2014   日本薬学会134年会   エベロリムスによるSTAT3活性化変動を介した間質性肺疾患発症機構の探索

    老川諒, 山本和宏, 宇田篤史, 中川勉, 平野剛, 平井みどり

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  • 安全医学賞(一般の部)最優秀賞受賞(共著)

    2011   第9回日本予防医学リスクマネージメント学会   薬品適正使用に向けて、薬剤師が臨床検査値を活用するための取り組み

    岡本千明, 山本和宏, 大本暢子, 五百蔵武士, 久米学, 槇本博雄, 平野剛, 楠信也, 古森孝英, 平井みどり

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Research Projects

  • 腎機能障害患者におけるがん薬物療法の新規用量設計法の確立に向けた生理学的薬物動態モデル&シミュレーションとビッグデータの統合解析

    2024.12 - 2026.11

    臨床薬理研究振興財団  学術奨励賞 

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    Authorship:Principal investigator 

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  • リアルワールドデータとゲノミクスの統合解析を通じた免疫療法誘発心筋炎の発症予測

    Grant number:24KK0173  2024.09 - 2028.03

    日本学術振興会  科学研究費助成事業  国際共同研究加速基金(海外連携研究)

    座間味 義人, 濱野 裕章, 新村 貴博, 松本 准, 小山 敏広, 山本和宏, 武田 達明

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    Authorship:Coinvestigator(s) 

    Grant amount:\20930000 ( Direct expense: \16100000 、 Indirect expense:\4830000 )

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  • データベーススクリーニングを活用した慢性腎臓病の新規治療標的の探索

    Grant number:24K09938  2024.04 - 2027.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    山本 和宏

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

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  • 周産期母児における抗精神病薬治療の適正化のためのファーマコメトリクス

    Grant number:22K06697  2022.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    矢野 育子, 山本 和宏

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

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  • 新生児における鎮静薬の科学的投与設計ノモグラムの開発に向けた PBPK モデル&シミュレーションの応用

    2022

    臨床薬理研究振興財団  2022 年度臨床薬理研究振興財団研究奨励金 

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    Authorship:Principal investigator 

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  • Strategy for prevention of interstitial lung disease induced by molecular targeted therapy.

    Grant number:19K07191  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Yamamoto Kazuhiro

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    Our clinical study demonstrated that the patients with specific genotype of signal transducer and activator of transcription 3 (STAT3) polymorphism have higher cumulative incidence of interstitial lung disease (ILD). Moreover, our basic study revealed that A549 cells, an alveolar epithelial cell line carried with ILD low-risk genotype, shown reduction of CXCL2 and enhancement of Akt activity by long-term exposure of everolimus in addition to induction of epithelial mesenchymal transition. These molecular expression and activity changes may be an important perception for the preventive strategy for ILD.

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  • Pharmacometrics in the clinical setting for dosage adjustment of special populations

    Grant number:16K08400  2016.04 - 2019.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Yano Ikuko, ITOHARA Kotaro, INOUE Miho, YAMAMOTO Kazuhiro

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    Grant amount:\4810000 ( Direct expense: \3700000 、 Indirect expense:\1110000 )

    In adult patients after living-donor liver transplantation (LDLT), postoperative days and CYP3A5 genotype are known to affect tacrolimus pharmacokinetics. We constructed a physiologically based pharmacokinetic (PBPK) model adapted to the clinical data, and evaluated the contribution of liver regeneration as well as hepatic and intestine CYP3A5 genotypes on tacrolimus pharmacokinetics. As a result, liver function recovered immediately and affected the total body clearance of tacrolimus during only limited periods after LDLT. The constructed PBPK model clarified the oral clearance of tacrolimus was affected by the CYP3A5 genotypes in both the liver and intestine to the same extent. The recommended initial dosage of tacrolimus guided by genotype using PBPK simulations would be useful to maintain the therapeutic range quickly.

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  • 薬剤性肺線維症の分子メカニズムの解明とゲノム薬理学的解析の統合的研究

    2016 - 2018

    日本学術振興会  科学研究費助成事業 基盤研究(C) 

    山本 和宏

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  • 腎細胞癌患者の分子標的治療における有効性マーカーのPK-PD統合的なPGx解析

    2015

    黒住医学研究振興財団  平成27年度(第23回)研究助成金 

    山本 和宏

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    Authorship:Principal investigator  Grant type:Competitive

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  • 分子標的治療薬による皮膚障害発症メカニズムに基づく新規予防・治療法の探索

    2014 - 2015

    日本学術振興会  科学研究費助成事業 若手研究(B) 

    山本 和宏

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    Authorship:Principal investigator  Grant type:Competitive

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  • エベロリムスによる口内炎の副作用バイオマーカーの探索

    2014

    ノバルティスファーマ株式会社  Novartis CPCF Research Grant 2014 

    山本 和宏

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    Authorship:Principal investigator  Grant type:Competitive

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  • 分子標的治療薬における間質性肺炎の新規バイオマーカーの統合的探索

    2014

    武田科学振興財団  2014年度薬学系研究奨励 

    山本 和宏

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    Authorship:Principal investigator  Grant type:Competitive

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  • The role of the mTOR signalling pathway in placental nutrient transport.

    Grant number:25460211  2013.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HIRANO TAKESHI, HIRAI Midori, YAMAMOTO Kazuhiro

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    Grant amount:\5200000 ( Direct expense: \4000000 、 Indirect expense:\1200000 )

    The mTOR pathway represents an important intracellular regulatory process between nutrient and amino acid transport in the human placenta. PI3K and mTOR pathway, a novel p110 interacting protein was identified by the protein-protein interactions using co-immunoprecipitation. We demonstrate the p110 catalytic subunit directly binds to mTORC1. These results suggested that P110 is important factor and the mTOR regulator. We suggest that mTOR signaling represents an important regulatory pathway for placental nutrient transporters.

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  • 6. 分子標的治療薬による皮膚障害のSTAT3を標的とした新規治療法の確立

    2013

    公益財団法人薬学研究奨励財団  平成25年度研究助成金 

    山本 和宏

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    Authorship:Principal investigator  Grant type:Competitive

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  • 分子標的治療薬の皮膚障害発症予測のためのゲノム薬理学的解析

    2013

    公益財団法人がん研究振興財団  平成25年度(第46回)がん研究助成金 

    山本 和宏

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    Authorship:Principal investigator  Grant type:Competitive

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  • 分子標的治療薬の皮膚障害における副作用マーカーのゲノム薬理学的解析

    2013

    公益財団法人政策医療振興財団  平成25年度研究助成 

    山本和宏

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    Authorship:Principal investigator  Grant type:Competitive

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  • Search for biomarkers of adverse events as skin reaction by molecular target drugs

    Grant number:24790156  2012 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    YAMAMOTO KAZUHIRO

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

    This study aimed to examine whether the toxicity of molecular target drugs for human keratinocytes was associated with inhibiting signal transducer and activator of transcription 3 (STAT3). We studied whether STAT3 activity affects molecular target drugs-induced cell growth inhibition in HaCaT cells by WST-8 assay. Stattic enhanced the cell-growth inhibitory and apoptotic effects of molecular target drugs. HaCaT cells transfected with constitutively- active STAT3 (STAT3C) were resistant to the molecular target drugs-induced cell growth inhibition. STAT3 activity decreased after short-term treatment with sorafenib and sunitinib in a dose-dependent manner and recovered after long-term treatment with molecular target drugs at low doses. Moreover, HaCaT cells transfected with STAT3C showed high expression of apoptosis suppressors, e.g. bcl-2 and survivin. Thus, STAT3 activation mediating apoptosis suppressors may be a key factor in molecular target drugs-induced keratinocyte cytotoxicity.

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  • 分子標的治療薬による皮膚障害発症メカニズムの分子生物学的解明

    2011

    公益財団法人中冨健康科学振興財団  平成22年度中冨健康科学振興財団研究助成 

    山本和宏

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    Authorship:Principal investigator  Grant type:Competitive

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