Updated on 2021/12/16

写真a

 
AIBA Tetsuya
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Associate Professor
Position
Associate Professor
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Degree

  • 博士(薬学) ( 京都大学 )

Research Interests

  • Bioavailability

  • 消化管吸収

  • Clinical Pharmacokinetics

  • 投与設計

  • 速度論

  • バイオアベイラビリティ

  • 薬物代謝

  • 薬物動態

Research Areas

  • Life Science / Clinical pharmacy

  • Life Science / Pharmacology

  • Life Science / Pharmaceutical chemistry and drug development sciences

Education

  • Kyoto University   薬学研究科   医療薬剤学

    - 1991

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    Country: Japan

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  • Kyoto University    

    - 1991

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  • Kyoto University    

    - 1987

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  • Kyoto University   薬学部   薬学科

    - 1987

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    Country: Japan

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Research History

  • - 岡山大学医歯薬学総合研究科 准教授

    2005

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  • - Associate Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2005

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Professional Memberships

  • 日本薬物動態学会

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  • 米国薬学会(American Association of Pramoceutical Scientists)

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  • 日本薬学会

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Papers

  • Acute peripheral inflammation increases plasma concentration of hypoglycemic agent nateglinide with decreased hepatic drug-metabolizing activity in rats. Reviewed

    Kojina M, Suzuki K, Nishiwaki A, Aiba T

    Biological and Pharmaceutical Bulletin   44 ( 1 )   96 - 102   2021.1

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

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  • Effects of dexamethasone to reverse decreased hepatic midazolam metabolism in rats with acute renal failure. Reviewed

    Doi M, Kajikawa N, Aiba T

    Xenobiotica   50 ( 5 )   506 - 514   2020.3

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

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  • In Vivo Study on Mechanism Underlying Increased Pharmacological Effects of Phenobarbital in Rats with Glycerol-Induced Acute Renal Failure Reviewed

    Atsuyoshi Okada, Keiichiro Suzuki, Keisuke Hara, Moeko Kojina, Tetsuya Aiba

    Biological and Pharmaceutical Bulletin   42 ( 3 )   501 - 506   2019.3

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Pharmaceutical Society of Japan  

    DOI: 10.1248/bpb.b18-00659

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  • Altered hepatic drug-metabolizing activity in rats suffering from hypoxemia with experimentally induced acute lung impairment Reviewed

    Yuki Hori, Yasumasa Shimizu, Tetsuya Aiba

    Xenobiotica   48 ( 6 )   576 - 583   2018.6

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Taylor and Francis Ltd  

    1.Hepatic drug-metabolizing activity was investigated in vitro with liver microsomes prepared from rats suffering from hypoxemia with experimentally induced acute lung impairment (ALI). 2.Male Wistar rats received an intrabronchial administration of dilute hydrochloride solution for ALI induction. Pooled liver microsomes were prepared for the normal and ALI rats, and the hepatic drug metabolism mediated by cytochrome P450 (CYP) 3 A was examined in an incubation study with the microsomes. 3.The NADPH-dependent metabolism of midazolam significantly increases in ALI rats as compared with that in normal rats. Testosterone 6β-hydroxylation was also observed to significantly increase in ALI rats. 4.When the hepatic expression of CYP3A proteins was examined, the protein expression of CYP3A1 was shown to significantly increase and that of CYP3A2 remained unaltered in ALI rats. The hepatic expression of NADPH-cytochrome P450 reductase (POR), a protein mediating electron transfer in CYP-mediated drug metabolism, was also revealed to significantly increases in ALI rats. 5.With the findings regarding the midazolam elimination, the hepatic drug-metabolizing activity seems to increase in response to acute hypoxemia, partly due to an altered expression of the CYP3A enzymes, and an augmented electron transfer with an increased POR expression is probably involved in the increase.

    DOI: 10.1080/00498254.2017.1349969

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  • Bortezomib combined with standard induction chemotherapy in Japanese children with refractory acute lymphoblastic leukemia Reviewed

    Akihiro Iguchi, Yuko Cho, Minako Sugiyama, Yukayo Terashita, Tadashi Ariga, Yosuke Hosoya, Shinsuke Hirabayashi, Atsushi Manabe, Keisuke Hara, Tetsuya Aiba, Tsugumi Shiokawa, Hiroko Tada, Norihiro Sato

    International Journal of Hematology   106 ( 2 )   291 - 298   2017.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER JAPAN KK  

    Bortezomib has been shown to be effective and well-tolerated in patients with refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not been evaluated in Japanese pediatric patients. Here, we report the results of a clinical trial designed to evaluate the safety of bortezomib combined with induction chemotherapy in Japanese children with refractory ALL. A total of six patients with B-precursor ALL were enrolled in this study. Four-dose bortezomib (1.3 mg/m(2)/dose) combined with two standard induction chemotherapies was used. Prolonged pancytopenia (grade 4) was observed in all patients. Four of the six patients developed severe infectious complications. Peripheral neuropathy (grade 2) occurred in five patients. The individual plasma bortezomib concentration-time profiles were not related to toxicity and efficacy. Five patients were evaluable for response, and four patients achieved complete response (CR) or CR without platelet recovery (80%). In conclusion, four-dose bortezomib (1.3 mg/m(2)/dose) combined with standard re-induction chemotherapy was associated with a high risk of infectious complications induced by prolonged neutropenia, although high efficacy has been achieved for Japanese pediatric patients with refractory ALL. Attention must be given to severe infectious complications when performing re-induction chemotherapy including bortezomib.

    DOI: 10.1007/s12185-017-2235-z

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  • Correlation between the Efficacy of Lamotrigine and the Serum Lamotrigine Level during the Remission Phase of Acute Bipolar II Depression: A Naturalistic and Unblinded Prospective Pilot Study Reviewed

    Akiyoshi Kikkawa, Yoshihisa Kitamura, Tetsuya Aiba, Koichi Hiraki, Toshiaki Sendo

    Biological and Pharmaceutical Bulletin   40 ( 4 )   413 - 418   2017.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PHARMACEUTICAL SOC JAPAN  

    Lamotrigine has acute antidepressant effects in patients with bipolar disorder. However, there is little information regarding appropriate serum levels of lamotrigine and the time until remission after the start of lamotrigine therapy in patients with bipolar II depression. This was a naturalistic and unblinded prospective pilot study. Twelve patients' depressive symptoms were evaluated using the Montgomery-angstrom sberg Depression Rating Scale (MADRS) at the start of treatment and at the time of remission, and blood samples were obtained at the time of remission. Mahalanobis distance was used to analyze the relationship between the MADRS improvement rate and the serum lamotrigine level. Furthermore, we calculated the Spearman's rank correlation coefficient for the relationship between the MADRS improvement rate and the serum lamotrigine level, and produced box plots of the serum lamotrigine level at remission and the time until remission. The Mahalanobis distance for the patient that was co-administered lamotrigine and valproic acid differed significantly from those of the other patients (p<0.001). There was no linear relationship between the serum lamotrigine level and the MADRS improvement rate among the patients that did not receive valproic acid. The median time from the start of lamotrigine therapy until remission was 6 weeks. The serum lamotrigine level does not have an important impact on the acute therapeutic effects of lamotrigine on bipolar II depression. In addition, we consider that different treatment options should be considered for non-responders who do not exhibit any improvement after the administration of lamotrigine for approximately 6 weeks.

    DOI: 10.1248/bpb.b16-00725

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  • Similarities of Water-soluble Vitamin Components among Non-prescription Pharmaceutical Vitamin Products Generally Available on the Domestic Market Reviewed

    Keiichiro Suzuki, Moeko Kojina, Tetsuya Aiba

    YAKUGAKU ZASSHI   137 ( 5 )   595 - 602   2017

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    Publishing type:Research paper (scientific journal)   Publisher:Pharmaceutical Society of Japan  

    DOI: 10.1248/yakushi.16-00227

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  • Altered hepatic drug metabolizing activity in rats with acute lung impairment

    Yuki Hori, Yasumasa Simizu, Tetsuya Aiba

    Drug Metabolism Reviews   47   89 - 89   2015.11

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    Language:English   Publisher:TAYLOR & FRANCIS LTD  

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  • In vivo application of chitosan to improve bioavailability of cyanocobalamin, a form of vitamin B-12, following intraintestinal administration in rats Reviewed

    Yuko Goto, Ayumi Masuda, Tetsuya Aiba

    International Journal of Pharmaceutics   483 ( 1-2 )   250 - 255   2015.4

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    The effect of chitosan on the intestinal absorption of cyanocobalamin (VB12), a stable form of vitamin B-12, was investigated in vivo in rats, with the aim of improving the oral bioavailability of VB12 for anemia treatment in patients with gastrectomy. The bioavailability was evaluated based on the plasma concentration profile of VB12 following intraintestinal administration of the VB12 solution containing chitosan at various concentrations. The bioavailability of VB12 was 0.6 +/- 0.2% when the chitosan-free VB12 solution was administered, while it increased to 10.5 +/- 3.3% when chitosan was dissolved in the VB12 solution at a concentration of 1%. The bioavailability of VB12 increases with the chitosan concentration, in which chitosan seems to augment the amount of VB12 absorbed without affecting the absorption rate constant of VB12. It was also shown that the bioavailability of VB12 does not increase further when the degree of chitosan deacetylation is increased from 83 to 100% by substitutively employing the fully deacetylated chitosan. These findings suggest that the oral administration of VB12 with readily available chitosan may be a practical approach for anemia treatment in patients with gastrectomy. (C) 2015 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.ijpharm.2015.02.016

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  • Pharmaceutical properties of a low-substituted hydroxypropyl cellulose (L-HPC) hydrogel as a novel external dressing Reviewed

    Atsushi Ogawa, Sachie Nakayama, Mami Uehara, Yasuhiro Mori, Mai Takahashi, Tetsuya Aiba, Yuji Kurosaki

    International Journal of Pharmaceutics   477 ( 1-2 )   546 - 552   2014.12

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

    Controlling the moisture balance between exudates and their transpiration from the surface of wounded skin is important for healing. Low-substituted hydroxypropyl cellulose (L-HPC) hydrogel sheets (HGSs) possessing high water retention and water vapor transmission properties were prepared by neutralizing the highly viscous alkaline liquid of 7-10% L-HPC. Glycerol-impregnated L-HPC hydrogel sheets (L-HPC G-HGSs) were obtained by exchanging aqueous liquid in L-HPC HGSs. The physical characteristics required for wound dressings, i.e., mechanical strength, adhesive strength, and water retention properties, as well as the water vapor transmission (WVT) properties of L-HPC HGSs and L-HPC G-HGSs were evaluated. The mechanical strengths of L-HPC HGSs were enhanced with increases in the L-HPC content. The impregnation of glycerol in L-HPC HGSs yielded a significantly elasticated sheet. The adhesive strengths of L-HPC HGSs were significantly lower than those of commercial medical dressings. Water retention in L-HPC HGSs after being stored for 2 h at 37 degrees C was approximately 50%. The WVT rate of 7% L-HPC HGS was approximately 40 g/m(2)/h, which was markedly higher than that of silicone gel type medical dressings. In conclusion, L-HPC HGSs are promising dressings that maintain an adequate moisture balance by transpiring excessive wound exudates with less damage to the healing wound. (C) 2014 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.ijpharm.2014.10.043

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  • 双極性障害II型患者のうつ状態急性期に対するラモトリギンの血中濃度と効果との関係および寛解までの服用日数に関する検討

    吉川明良, 吉川明良, 北村佳久, 合葉哲也, 和田健, 森田幸孝, 岩本崇志, 開浩一, 千堂年昭

    臨床薬理   45 ( Supplement )   S250 - S250   2014.11

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    Language:Japanese   Publisher:(一社)日本臨床薬理学会  

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  • Effect of Carrageenan-induced Acute Peripheral Inflammation on the Pharmacokinetics and Hepatic Metabolism of Midazolam in Rats Reviewed

    Noriko Kajikawa, Masami Doi, Jun-ichi Kusaba, Tetsuya Aiba

    Drug Metabolism and Pharmacokinetics   29 ( 5 )   400 - 406   2014.10

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    The effect of carrageenan-induced acute peripheral inflammation (API) on the pharmacokinetics of the hepatically metabolizing compound midazolam (MDZ) was investigated in rats. Rats were subcutaneously treated with lambda-carrageenan in the hind paw to induce API. When MDZ was intravenously administered in male rats, it was demonstrated that the plasma concentration profile of MDZ slightly alters in API rats compared with that in normal rats, while the plasma concentrations of its metabolites, 4-hydroxy and 1'-hydroxy MDZ, are markedly reduced with delayed appearances in API rats. In the incubation study with rat liver microsomes, it was clearly indicated that the generation rates of the two metabolites decrease in API rats. Western blot analysis revealed that hepatic CYP3A1 expression increases, while CYP3A2 expression decreases in API rats. In female rats, in which CYP3A2 is barely expressed in the liver, MDZ metabolism is little affected by API. These findings indicate that the hepatic handling of a therapeutic compound varies with API, largely due to altered hepatic expression of the drug-metabolizing enzyme.

    DOI: 10.2133/dmpk.DMPK-14-RG-020

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  • Interspecies comparison of hepatic metabolism of six newly synthesized retinoid X receptor agonistic compounds possessing a 6-[N-ethyl-N-(alkoxyisopropylphenyl)amino]nicotinic acid skeleton in rat and human liver microsomes Reviewed

    Yoshiki Murakami, Yasumasa Shimizu, Akemi Ogasawara, Satoshi Ueshima, Mariko Nakayama, Kohei Kawata, Hiroki Kakuta, Tetsuya Aiba

    Drug Development and Industrial Pharmacy   40 ( 8 )   1065 - 1071   2014.8

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:INFORMA HEALTHCARE  

    Objective: The hepatic metabolism of six compounds newly synthesized as retinoid X receptor agonists was characterized in rat and human liver microsomes to examine the relationship between their hepatic metabolism profiles and side chain structures, considering the interspecies difference.
    Materials and methods: The compounds used have a 6-[N-ethyl-N-(3-alkoxy-4-isopropylphenyl)amino]nicotinic or 6-[N-ethyl-N-(4-alkoxy-3-isopropylphenyl)amino]nicotinic acid skeleton, in which the isopropoxy, isobutoxy or cyclopropylmethoxy group is employed for the alkoxy group. These compounds were incubated with the microsomes, and their Michaelis-Menten parameters were determined. The incubation study was also performed with various cytochrome P450 (CYP) inhibitors to examine their susceptibilities to the inhibitors. In addition, a molecular docking simulation was conducted to assess the compound's spatial configuration with the CYP isoform when necessary.
    Results: The Michaelis-Menten parameters determined are comparable between rats and humans for the compounds having 3-isobutoxy, 4-isobutoxy, 4-isopropoxy and 4-cyclopropylmethoxy groups. However, it was indicated that all compounds except that having the 3-isobutoxy group are metabolized in a different manner between rats and humans. That is, the extent of the contribution of each CYP isozyme is different between those two species. A molecular docking simulation showed that the spatial configuration of the compound to be associated with CYP2D6 markedly changes depending on whether the isobutoxy group is situated at the 3- or 4-position.
    Conclusion: A slight difference in the side chain structures markedly alters the compound's metabolic profile, which amplifies the interspecies difference regarding the profile, increasing the difficulty in characterizing the profile in humans with the structural-property relationship and interspecies extrapolation.

    DOI: 10.3109/03639045.2013.807278

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  • Utility of simple suspension method compared to loss of drug using crushing method on tube administration

    ZAMAMI YOSHITO, KOYAMA TOSHIHIRO, AIBA TETSUYA, AMANO MANABU, ANDO TETSUAKI, KURATA NAOMI, NAWA HIDEKI, NAKURA HIRONORI, KITAMURA YOSHIHISA, SENDO TOSHIAKI

    静脈経腸栄養   29 ( 4 )   1027-1033 (J-STAGE) - 1033   2014.7

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    【目的】従来の薬剤経管投与法である粉砕法は薬効の減少につながる薬剤量の損失が指摘されている。そこで粉砕法による薬剤量損失に対する簡易懸濁法の有用性について検討した。【方法】頻繁に粉砕指示がなされる5種類の薬剤を用いて粉砕・分包による薬物含量減少、薬剤調製時の懸濁性および実際の経管投与を想定した薬物含量について2つの方法を比較した。【結果】薬剤を粉砕・分包するとそれぞれの薬物含量は減少した。またワーファリン錠を粉砕して水に溶解すると完全には懸濁せず、小さな塊が生じたが、簡易懸濁法では均一に懸濁した。ワーファリン錠の経管投与を想定した実験において粉砕法では薬物含量が大幅に減少したが、簡易懸濁法では、ほとんど損失が認められなかった。【結論】簡易懸濁法は粉砕法に比べて薬剤損失の面で有用性が高いことが示唆され、ワーファリン錠のように安定性が悪い薬剤では特に適正な薬物投与に貢献出来ると考えられる。(著者抄録)

    DOI: 10.11244/jjspen.29.1027

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  • Effects of Peritoneal Dialysis on Pharmacotherapy: A Deductive Pharmacokinetic-model Approach to Predict Drug Concentration Profiles in Plasma and Peritoneal Fluid Reviewed

    Mizuki Horiuchi, Soichiro Moriyama, Yukiko Takahata, Tetsuya Aiba, Yuji Kurosaki

    Drug Metabolism and Pharmacokinetics   29 ( 2 )   154 - 161   2014.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:JAPANESE SOC STUDY XENOBIOTICS  

    The aim of this study was to present a deductive compartment pharmacokinetic (PK) model to predict the concentration profiles of drugs in plasma and peritoneal fluid in peritoneal dialysis (PD) rats. PK parameters of model drugs in normal and experimentally induced acute renal failure (ARF) rats not undergoing PD were obtained inductively in a common regression manner with a two-compartment model. In PD normal and ARF rats, PK parameters relating to the transfer of drugs to the peritoneal dialysate and the progress of renal failure were deductively modified to simulate the drug concentration-time profiles in plasma and in the peritoneal fluid in PD rats. The deductively introduced modifiers were the volume of distribution in the peripheral compartment, plasma protein binding, and solvent movement factor to the peritoneal fluid. Predicted profiles of tolbutamide, propranolol and cefazolin in PD normal and ARF rats were compared with the corresponding observed data. This minimal deductive approach yielded satisfactory accuracy in the prediction of both the plasma and peritoneal fluid concentrations of tolbutamide and propranolol.

    DOI: 10.2133/dmpk.DMPK-13-RG-067

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  • 双極性障害患者に対するラモトリギンの使用実態調査と考察

    Akiyoshi Kikkawa, Yoshihisa Kitamura, Ken Wada, Yukitaka Morita, Takashi Iwamoto, Tetsuya Aiba, Kouiti Hiraki, Toshiaki Sendou

    日本病院薬剤師会雑誌   50 ( 4 )   491 - 494   2014

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  • 遮光器具を用いた光に不安定な薬剤の含量減少の抑制について

    座間味義人, 座間味義人, 座間味義人, 東恩納司, 安藤哲信, 武藤浩司, 天野学, 倉田なおみ, 合葉哲也, 北村佳久, 千堂年昭

    静脈経腸栄養   29 ( 3 )   SUP54(J-STAGE)   2014

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  • Effect of Carrageenan-Induced Acute Peripheral Inflammation on the Electrolyte Disposition to Cerebrospinal Fluid in Rats Reviewed

    Kentaro Kono, Atsuyoshi Okada, Atsuko Ishikawa, Tetsuya Aiba

    Biological and Pharmaceutical Bulletin   36 ( 11 )   1829 - 1834   2013.11

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:PHARMACEUTICAL SOC JAPAN  

    To clarify whether peripheral inflammation has a remote effect on the central nervous system, the electrolyte disposition between the circulating blood and central nervous system was evaluated in rats with carrageenan-induced acute peripheral inflammation (API). lambda-Carrageenan was subcutaneously injected in the hind paw of the rat, and lithium was utilized as a surrogate marker of sodium. When the plasma and cerebrospinal fluid (CSF) concentrations of lithium were examined following lithium being intravenously administered, it was revealed that the CSF concentration of lithium in API rats is reduced compared to that in normal rats, while the plasma concentration profile of lithium in API rats is indistinguishable from that in normal rats. The pharmacokinetic analysis showed that the lithium disposition from the plasma to CSF markedly decreased by 35.8% in API rats compared to that in normal rats. On the other hand, when lithium was immediately administered into the lateral ventricle, its elimination profiles in CSF were not different between normal and API rats. It is therefore probable that the lithium disposition from the plasma to CSF alters in API rats, reflecting the entry process of electrolytes from the circulating blood to brain tissue being suppressed in response to peripheral inflammation.

    DOI: 10.1248/bpb.b13-00531

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  • 双極性障害患者に対するラモトリギンの使用実態調査と考察

    吉川明良, 北村佳久, 合葉哲也, 和田健, 森田幸孝, 岩本崇志, 開浩一, 千堂年昭

    日本医療薬学会年会講演要旨集   23rd   433   2013.8

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  • The Effects of Body Weight and Combination Drug Therapy on the Serum Concentrations of Zonisamide in 94 Epileptic dogs: An Epidemiological Analysis Reviewed

    Koya Fukunaga, Tetsuya Aiba, Miyoko Saito, Makoto Muto, Naoyuki Watanabe, Keiko Uchida, Seiichi Okuno, Takayuki Kobayashi, Kensuke Orito

    International Journal of Appled Research in Veterinary Medicine   10 ( 3 )   258 - 263   2012.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:VETERINARY SOLUTIONS LLC  

    To clarify the effects of background factors such as body weight, combination drug therapy with phenobarbital (PB) and potassium bromide (KBr), age, gender, neuter status, and blood collection time on the serum concentrations of zonisamide (ZNS) in 94 epileptic dogs, serum ZNS concentrations of 141 samples from 94 epileptic dogs were measured by high-performance liquid chromatography with UV detection. Serum ZNS concentrations were divided by the dosage of ZNS, to obtain normalized ZNS concentrations. Multiple linear regression analysis revealed that body weight and combination therapies with KBr, PB, and KBr + PB affected the normalized ZNS concentrations, and normalized ZNS concentrations were positively correlated with body weight. The normalized ZNS concentrations in dogs with PB combination therapy were lower when compared with those concentrations in dogs receiving ZNS alone, but were higher in dogs receiving KBr combination therapy. These results suggest that serum ZNS concentrations are influenced by body weight and combination drug therapies using KBr, PB, and KBr + PB. This information of ZNS characteristics may be useful in determining the initial and modified doses of ZNS in the therapy of epileptic dogs.

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  • In Vivo Application of Chitosan to Facilitate Intestinal Acyclovir Absorption in Rats Reviewed

    Ayumi Masuda, Yuko Goto, Yuji Kurosaki, Tetsuya Aiba

    Journal of Pharmaceutical Sciences   101 ( 7 )   2449 - 2456   2012.7

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    The effect of chitosan on the intestinal absorption of acyclovir (ACV) was evaluated in rats, and factors influencing its facilitative effect on the ACV absorption were examined. When ACV solution containing 1% chitosan with an average molecular weight of 150 kDa was administered into the upper jejunum, a significant increase in the plasma ACV concentration was observed, with the peak ACV concentration being eight times greater than that observed with the chitosan-free solution. The chitosan-free ACV solution, whose viscosity was adjusted to remain unchanged with polyethylene glycol, did not cause an increase in the plasma concentration, and neither did the chitosan-free solutions substitutionally containing low molecular cationic compounds, triethanolamine and kanamycin. When chitosan was digested with chitosanase to shorten its polycationic polysaccharide structure, chitosan subjected to 150-min digestion retained its facilitative effect on ACV absorption, but that subjected to 420-min digestion no longer caused facilitation, in which its average molecular weight was reduced to around 10 kDa. It is therefore indicated that intestinal ACV absorption can be facilitated with chitosan, and that it is necessary for chitosan to have a certain length of polycationic polysaccharide structure to exert such facilitation. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2449-2456, 2012

    DOI: 10.1002/jps.23170

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  • 新規RXRアゴニスト及びその類縁化合物のヒト肝における代謝特性の予測

    合葉 哲也, 村上 由樹, 清水 康正, 川田 浩平, 中山 真理子, 小笠原 明美, 岡田 淳芳, 黒崎 勇二, 加来田 博貴

    日本薬学会年会要旨集   132年会 ( 2 )   269 - 269   2012.3

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  • Comparative study on altered hepatic metabolism of CYP3A substrates in rats with glycerol-induced acute renal failure Reviewed

    Jun-ichi Kusaba, Noriko Kajikawa, Hiromu Kawasaki, Yuji Kurosaki, Tetsuya Aiba

    Biopharmaceutics and Drug Disposition   33 ( 1 )   22 - 29   2012.1

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    To examine the mechanism accounting for the diverse alteration of hepatic metabolism of CYP3A substrates observed with renal function being severely impaired, the hepatic drug metabolizing activity was evaluated using liver microsomes prepared from rats with glycerol-induced acute renal failure (ARF). Midazolam, nifedipine and rifabutin were employed as representative CYP3A substrates. When the Michaelis-Menten parameters, Km and Vmax, were examined in the incubation study, the Km values of midazolam and nifedipine in ARF rats were shown to decrease by 50.9% and 29.9% compared with the normal value, respectively. The Vmax values of midazolam and nifedipine in ARF rats also decreased by 49.3% and 28.0%, respectively, showing that their decreased Km values accompanied the decreased Vmax values. The parameters of nifedipine seemed to alter to a lesser extent than those of midazolam. As for rifabutin metabolism, the decrease in the Km value was observed in ARF rats, but it did not accompany the decrease in the Vmax value. Then, the hepatic expressions of the CYP3A subfamily were examined with western blotting using anti-CYP3A1 and anti-CYP3A2 antibodies. It was revealed that the hepatic expression of CYP3A2 decreased, while that of CYP3A1 was unaffected. Additionally, a band signal deduced to originate from CYP3A9 was clearly detected in ARF, but not in normal rats. Considering each substrate having different specificities for CYP3A subfamily member proteins, individual alterations of hepatic CYP3A subfamily expression seem to underlie the diverse alterations of hepatic metabolism of CYP3A substrates in ARF rats. Copyright (C) 2012 John Wiley & Sons, Ltd.

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  • 肺移植患者におけるシクロスポリン経口クリアランスに及ぼす移植後経過日数の影響

    土井原 夕貴, 上島 智, 合葉 哲也, 佐藤 智昭, 河崎 陽一, 山根 正修, 大藤 剛宏, 松永 尚, 黒崎 勇二, 三好 新一郎, 千堂 年昭

    臨床薬理   42 ( Suppl. )   S268 - S268   2011.10

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  • P-0589 経腸栄養剤を用いた疎水性薬剤の簡易懸濁法適用の検討(一般演題 ポスター発表,医薬品情報・データベース,Enjoy Pharmacists' Lifestyles)

    座間味 義人, 松永 康臣, 合葉 哲也, 天野 学, 小山 敏広, 四宮 一昭, 北村 佳久, 黒崎 勇二, 佐々木 健二, 野田 真吾, 千堂 年昭, 川崎 博己, 五味田 裕

    日本医療薬学会年会講演要旨集   21   2011.9

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  • Pharmacodynamic Characterization of Nitric Oxide-Mediated Vasodilatory Activity in Isolated Perfused Rat Mesenteric Artery Bed Reviewed

    Shinsuke Inoue, Tetsuya Aiba, Yasuyuki Masaoka, Keiko Shimizu, Yukiko Komori, Mitsunobu Mio, Shingo Takatori, Hiromu Kawasaki, Yuji Kurosaki

    Biological and Pharmaceutical Bulletin   34 ( 9 )   1487 - 1492   2011.9

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    Vasodilation profiles following a short-term infusion of nitric oxide (NO), acetylcholine (ACh), and sodium nitroprusside (SNP) into an isolated perfused mesenteric artery bed were analyzed in rats to examine their vasodilatory efficacy under physiological conditions. These compounds commonly increase the intracellular NO concentration to exert vasodilatory activity. In an experiment with exogenous NO infusion where 100 mu l of 1 : 300 diluted NO-saturated solution (approx. 53 pmol of NO) was applied, the infusion caused transient vasodilation in a dose-dependent manner, with the peak vasodilation value being 74.7% of the maximum relaxation value. In experiments with ACh, the peak vasodilation value was 81.5% of the maximum at a dose of 60 pawl. The vasodilation profile of ACh was similar to that of NO infusion, but the ACh-induced vasodilation reduced at a slower rate than that induced by NO infusion. The vasodilatory activity of SNP was less potent than that of ACh, and its peak value was 62.8% of the maximum at a dose of 2000 pmol. However, SNP activity was augmented by removing the vascular endothelia of the mesenteric artery bed, and the peak value reached 67.3% of the maximum at a dose of 60 pmol. Pharmacodynamic analysis indicated that NO and ACh are equivalent regarding their vasodilator), efficacy, while the efficacy of SNP was less than 1% of theirs, as the arterial vascular endothelium impeded intracellular SNP-related NO generation, by which 95% of SNP's vasodilator), efficacy was negated. These findings will be helpful to understand factors influencing the therapeutic efficacy of vasodilators.

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  • Pharmacokinetic properties of newly synthesized retinoid X receptor agonists possessing a 6-[N-ethyl-N-(3-alkoxy-4-isopropylphenyl)amino]nicotinic acid skeleton in rats Reviewed

    Akemi Ogasawara, Yoshiki Murakami, Nobumasa Yakushiji, Fuminori Ohsawa, Jun-ichi Kusaba, Tetsuya Aiba, Yuji Kurosaki, Hiroki Kakuta

    Drug Development and Industrial Pharmacy   37 ( 9 )   1060 - 1067   2011.9

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    Objective: The pharmacokinetic properties of three newly synthesized retinoid X receptor (RXR) agonists were evaluated in rats to elucidate the structural factor influencing their pharmacokinetic properties. Material and methods: Three RXR agonists possessing a common 6-[N-ethyl-N-(3-alkoxy-4-isopropylphenyl)amino]nicotinic acid skeleton and side chain structures that are slightly different from each other were prepared as we previously reported (Takamatsu et al., ChemMedChem, 2008; 3: 780-787). The plasma concentration profiles of these compounds were evaluated following the intravenous and intra-intestinal administrations. Their hepatic metabolism was characterized using rat liver microsomes. Results: Based on the plasma concentration profile, NEt-3IP (3-isopropoxy) was shown to have a distribution volume of 4.53 L/kg, and to be cleared from the body with an elimination half-time of 0.95 h. The bioavailability of NEt-3IP is 16.4%, whereas those of the isobutoxy analog NEt-3IB and the cyclopropylmethoxy analog NEt-3cPM are 46.5% and 22.6%, respectively. Subsequently, in the experiments using rat liver microsomes, the K-m and V-max values of NEt-3IP were determined as 7.85 mu M and 0.48 nmol/min/mg protein, respectively. This K-m value is nearly the same as those of NEt-3IB and NEt-3cPM, but the V-max value is noticeably smaller. Additionally, it was revealed that the CYP family mainly metabolizing NEt-3IP is different from those metabolizing the other analogs. Conclusion: Based on these findings, the pharmacokinetic properties of the compounds possessing this type of the skeleton seem to be largely influenced by a slight modification of the side chain structure.

    DOI: 10.3109/03639045.2011.559247

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  • 肺移植患者におけるタクロリムス血中濃度推移の母集団解析

    上島 智, 合葉 哲也, 佐藤 智昭, 河崎 陽一, 山根 正修, 大藤 剛宏, 松永 尚, 黒崎 勇二, 三好 新一郎, 千堂 年昭

    TDM研究   28 ( 3 )   s180 - s180   2011.6

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  • Empirical Approach for Improved Estimation of Unbound Serum Concentrations of Valproic Acid in Epileptic Infants by Considering Their Physical Development Reviewed

    Satoshi Ueshima, Tetsuya Aiba, Tomoaki Sato, Hisashi Matsunaga, Yuji Kurosaki, Yoko Ohtsuka, Toshiaki Sendo

    Biological and Pharmaceutical Bulletin   34 ( 1 )   108 - 113   2011.1

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    The unbound serum concentration of valproic acid (VPA) is closely related to its therapeutic efficacy. In epileptic infants, the unbound VPA concentration varies largely from patient to patient, being difficult to predict using the reported equations for older children. To establish an equation to estimate the unbound concentration in infants, we empirically characterized the relationship between total and unbound VPA concentrations, taking their growth and development into consideration. Data were retrospectively collected from archived clinical records of 30 epileptic infants aged 0-11 months old. The relationship between total and unbound VPA concentrations was analyzed according to the Langmuir equation, in which the patient's body weight, height, and body surface area were considered as physical development indices. Inter- and intra-individual variabilities in the VPA concentrations were also considered. It was shown that the unbound VPA concentration in infants is properly estimated when their body weights are taken into account, in which the parameter for the maximum binding site concentration (Bm) increases as the body weight increases, while that for the dissociation constant (Xd) is unaltered. Additionally, the relationship was shown to slightly change when the infants are concomitantly treated with VPA and the other antiepileptics. These findings provide useful information to adjust the VPA dosage to achieve optimal therapeutic efficacy in epileptic infants.

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  • いま求められる薬剤師の教育力

    調剤と情報   17 ( 1 )   17 - 18   2011

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  • ジェネリック医薬品使用・銘柄変更ガイダンス(第二版) Reviewed

    合葉哲也, 出石啓治, 飯島康典, 岩月進, 加藤久幸, 小林大高, 坂巻弘之

    日本薬剤師会雑誌   63 ( 8 )   947 - 953   2011

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  • Altered Electrolyte Handling of the Choroid Plexus in Rats with Glycerol-induced Acute Renal Failure Reviewed

    Atsuko Ishikawa, Kentaro Kono, Rie Sakae, Tetsuya Aiba, Hiromu Kawasaki, Yuji Kurosaki

    Biopharmaceutics and Drug Disposition   31 ( 8-9 )   455 - 463   2010.11

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    The altered electrolyte handling of the choroid plexus was investigated in rats with acute renal failure (ARF) using lithium and rubidium as surrogate markers for sodium and potassium, respectively. Firstly, the transport of these two markers from the plasma to cerebrospinal fluid (CSF) was evaluated after they were concurrently injected into the femoral vein. As a result, their disposition from the plasma to CSF was shown to decrease in ARF rats, but the relationship profile between those two markers was not different from that observed in normal rats, indicating that the decreased disposition of lithium and rubidium occurs without affecting the stoichiometric balance. To clarify the mechanisms accounting for the decreased disposition, an inhibition study was then performed. When bumetanide, an inhibitor of the Na+/K+/2Cl(-) co-transporter, was directly introduced into the cerebroventricle prior to lithium and rubidium being intravenously administered, a marked increase in the markers' disposition was observed. However, such an increased disposition did not occur when bumetanide was injected into the femoral vein. Other inhibitors, such as amiloride for the Na+/H+ exchanger and ouabain for Na+/K+-ATPase, did not show any effects on marker disposition regardless of the inhibitor being administered into either the cerebroventricle or femoral vein. These findings suggest that the decreased marker disposition in ARF rats is due to an increased efflux process of the choroid plexus mediated by the Na+/K+/2Cl(-) co-transporter. That is, electrolyte efflux from the CSF to plasma increases, and thereby the electrolyte influx from the plasma to CSF is counteracted. Copyright (C) 2010 John Wiley & Sons, Ltd.

    DOI: 10.1002/bdd.726

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  • 小児におけるテイコプラニンの母集団薬物動態解析 血中濃度に及ぼす基礎疾患の影響

    槇田 崇志, 上島 智, 佐藤 智昭, 合葉 哲也, 黒崎 勇二, 松永 尚, 千堂 年昭

    TDM研究   27 ( 3 )   s155 - s155   2010.6

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  • 小児てんかん患者を対象としたバルプロ酸血中遊離型濃度の予測精度評価

    小松 仁美, 上島 智, 佐藤 智昭, 松永 尚, 合葉 哲也, 黒崎 勇二, 大塚 頌子, 千堂 年昭

    TDM研究   27 ( 3 )   s191 - s191   2010.6

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  • 簡易懸濁用容器「けんだくん」を用いた光に不安定な薬剤の含量減少の抑制について

    座間味義人, 東恩納司, 安藤哲信, 武藤浩司, 天野学, 倉田なおみ, 合葉哲也, 北村佳久, 松永尚, 千堂年昭, 黒崎勇二, 佐々木健二, 川崎博己, 五味田裕

    日本薬学会年会要旨集   130th ( 4 )   284   2010.3

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  • 新規骨格を有するRXRアゴニストの体内動態に関する基礎的検討

    村上 由樹, 小笠原 明美, 大澤 史宜, 合葉 哲也, 川崎 博己, 加来田 博貴, 黒崎 勇二

    日本薬学会年会要旨集   130年会 ( 4 )   265 - 265   2010.3

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  • 血管平滑筋弛緩作用の薬力学モデル解析

    合葉 哲也, 井上 真輔, 正岡 康幸, 清水 けい子, 小森 有希子, 高取 真吾, 見尾 光康, 川崎 博己, 黒崎 勇二

    日本薬学会年会要旨集   130年会 ( 4 )   265 - 265   2010.3

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  • Population Pharmacokinetic Analysis of Vancomycin Using Serum Cystatin C as a Marker of Renal Function Reviewed

    Akihiro Tanaka, Tetsuya Aiba, Takashi Otsuka, Katsuya Suemaru, Tatsuya Nishimiya, Tomoyoshi Inoue, Mitsuharu Murase, Yuji Kurosaki, Hiroaki Araki

    Antimicrobial Agents and Chemotherapy   54 ( 2 )   778 - 782   2010.2

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    We determined the population pharmacokinetics of vancomycin (VAN) using the glomerular filtration rate (GFR) estimated from the serum cystatin C concentration. We examined the predictive performance of the trough serum VAN concentration for determination of the initial dose by using a new model for the analysis of the population pharmacokinetic parameters. Data for 86 patients were used to estimate the values of the population pharmacokinetic parameters. Analysis with a nonlinear mixed-effects modeling program was done by using a one-compartment model. Data for 78 patients were used to evaluate the predictive performance of the new model for the analysis of population pharmacokinetic parameters. The estimated GFR values determined by using Hoek's formula correlated linearly with VAN clearance (VAN clearance [ml/min] = 0.825 x GFR). The mean volume of distribution was 0.864 (liters/kg). The interindividual variability of VAN clearance was 19.8%. The accuracy of the prediction determined by use of the new model was statistically better than that determined by use of the Japanese nomogram-based model because the 95% confidence interval (-3.45 to -1.38) of the difference in each value of the mean absolute error (-2.41) did not include 0. Use of the serum cystatin C concentration as a marker of renal function for prediction of serum VAN concentrations may be useful.

    DOI: 10.1128/AAC.00661-09

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  • 乳児を対象としたバルプロ酸血中遊離型濃度の母集団解析

    上島 智, 合葉 哲也, 佐藤 智昭, 松永 尚, 黒崎 勇二, 大塚 頌子, 千堂 年昭

    臨床薬理   40 ( Suppl. )   S242 - S242   2009.11

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  • ヨード造影剤と相互作用を有する薬剤に対するリスクマネジメント

    清水 けい子, 勝部 理早, 岡崎 宏美, 千堂 年昭, 合葉 哲也, 黒崎 勇二

    日本医療薬学会年会講演要旨集   19   2009.9

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  • Poor applicability of estimation method for adults to calculate unbound serum concentrations of valproic acid in epileptic neonates and infants Reviewed

    S. Ueshima, T. Aiba, N. Ishikawa, T. Sato, H. Kawasaki, Y. Kurosaki, Y. Ohtsuka, T. Sendo

    Journal of Clinical Pharmacy and Therapeutics   34 ( 4 )   415 - 422   2009.8

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    Objective:
    To characterize the relationship between total and unbound concentrations of valproic acid (VPA) in epileptic neonates and infants, the clinical examination records of those patients archived via therapeutic drug monitoring (TDM) activities were retrospectively analyzed.
    Methods:
    The screening encompassed 249 records of 114 epileptic patients aged 0-19 years old, who were treated with VPA monotherapy and whose total and unbound VPA concentrations were determined. These data were divided into groups according to the patients' age. In each group, the relationship between total and unbound VPA concentrations was compared to a reference profile, and the deviation from the reference was evaluated. The reference profile was calculated using the Langmuir equation, in which two parameters Kd and Bm were set to 7 center dot 8 and 130 mu g/mL, respectively, according to our previous findings.
    Results:
    The relationship between total and unbound VPA concentrations of patients of 0 years old considerably deviated from the reference, and their unbound VPA concentrations were generally higher compared to the corresponding reference values. It is suggested that the large deviation is related to the fact that the serum albumin concentrations of patients younger than 1 year old tend to be lower than those of patients in other age groups.
    Conclusion:
    Since the relationship between the VPA concentrations of epileptic neonates and infants is noticeably different from the reference, the unbound serum VPA concentrations of these patients are not adequately estimated using the same method as that for grown-ups. The unbound VPA concentrations of neonates and infants should be explicitly determined via TDM activities.

    DOI: 10.1111/j.1365-2710.2009.01022.x

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  • 乳児を対象としたバルプロ酸血中遊離型濃度の高精度推定式の構築

    上島 智, 合葉 哲也, 佐藤 智昭, 川崎 博己, 黒崎 勇二, 大塚 頌子, 松永 尚, 千堂 年昭

    TDM研究   26 ( 3 )   s161 - s161   2009.6

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  • 新規レチノイドX受容体アゴニストNEt-3IPのラットにおける体内動態評価

    小笠原 明美, 薬師寺 信匡, 合葉 哲也, 川崎 博己, 黒崎 勇二, 加来田 博貴

    日本薬学会年会要旨集   129年会 ( 4 )   220 - 220   2009.3

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  • Efficacy of Peritoneal Dialysis of Tolbutamide in Rats Under Conditions of the Plasma Unbound Fraction Being Increased Reviewed

    Takashi Makita, Tetsuya Aiba, Yuki Izuwa, Yukiko Komori, Hiromu Kawasaki, Yuji Kurosaki

    Biopharmacutics and Drug Disposition   30 ( 1 )   1 - 8   2009.1

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    Peritoneal dialysis of a highly protein-bound compound, tolbutamide, was examined in rats to clarify whether the efficacy of the peritoneal dialysis of such compounds increases proportionally as their unbound fractions increase. As expected, it was shown that the tolbutamide concentration of the peritoneal dialysate rose as the unbound fraction of tolbutamide increased. However, the efficacy of peritoneal dialysis of tolbutamide was proportionally elevated only when the unbound fraction was slightly increased by sulfa methoxazol e treatment. When the unbound fraction of tolbutamide was increased 7.8 times by sulfa dimethoxin e treatment, the dialysis efficacy was increased to only 58% of that expected. This discrepancy between the observed and expected values regarding dialysis efficacy was more marked when experiments were performed in rats with experimentally induced acute renal failure. Pharmacokinetic analysis indicated that the intrinsic dialysis clearance of tolbutamide decreased when its unbound fraction was greatly increased. These findings suggest that peritoneal dialysis may be mediated not only by passive diffusion, but also by concentration-dependent processes. The efficacy of the peritoneal dialysis of therapeutic compounds may be overestimated if the estimation is based only on their unbound fraction measured under control conditions. Copyright (C) 2009 John Wiley & Sons, Ltd.

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  • Comparative Study of Increased Plasma Quinidine Concentration in Rats with Glycerol- and Cisplatin-induced Acute Renal Failure Reviewed

    Yuki Izuwa, Jun-ichi Kusaba, Mizuki Horiuchi, Tetsuya Aiba, Hiromu Kawasaki, Yuji Kurosaki

    Drug Metabolism and Pharmacokinetics   24 ( 5 )   451 - 457   2009

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    A comparative study of altered plasma concentration of quinidine in rats with glycerol- and cisplatin-induced acute renal failure (ARF) was conducted with quinidine used as a positively charged and liver-metabolized therapeutic compound. Although apparent total body clearance of quinidine decreased to 68 and 48% of the normal value in glycerol- and cisplatin-induced ARF rats, respectively, its distribution decreased only in glycerol-induced ARF rats. The plasma unbound fraction of quinidine decreased in glycerol-induced ARF rats, which was not observed in cisplatin-induced ARF rats. The plasma level of alpha(1)-acid glycoprotein (AGP) increased in glycerol-induced ARF, but not in cisplatin-induced ARF rats. It is therefore conceivable that the plasma concentration of positively charged and liver-metabolized compounds generally increases due to hepatic elimination suppressed as renal function decreases, but the pharmacokinetic impact of suppressed hepatic elimination is occasionally difficult to observe in some ARF model rats since it may be blurred by the influence of increased plasma AGP level.

    DOI: 10.2133/dmpk.24.451

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  • Decreased lithium disposition to cerebrospinal fluid in rats with glycerol-induced acute renal failure Reviewed

    Rie Sakae, Atsuko Ishikawa, Tomoko Niso, Yukiko Komori, Tetsuya Aiba, Hiromu Kawasaki, Yuji Kurosaki

    Pharmaceutical Research   25 ( 10 )   2243 - 2249   2008.10

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    Purpose. The lithium disposition to cerebrospinal fluid (CSF) was evaluated in rats with acute renal failure (ARF) to examine whether electrolyte homeostasis of the CSF is perturbed by kidney dysfunction. In addition, the effects of renal failure on choroid plexial expressions of the Na+-K+-2Cl(-) co-transporter (NKCC1) and Na+/H+ exchanger (NHE1) were also studied.
    Methods. After lithium was intravenously administered at a dose of 4 mmol/kg, its concentration profile in plasma was evaluated by collecting plasma specimens, while that in CSF was monitored with a microdialysis probe in the lateral ventricles. NKCC1 and NHE1 expressions were measured via the Western immunoblot method using membrane specimens prepared from the choroid plexus in normal and ARF rats.
    Results. The lithium concentration in CSF of ARF rats was 30% lower than that of normal rats, while their plasma lithium profiles were almost the same, indicating that the lithium disposition to CSF was decreased in ARF rats. It was revealed that the choroid plexial expression of NKCC1 was increased by 40% in ARF rats, but that of NHE1 was unchanged.
    Conclusion. ARF decreases the lithium disposition to CSF, possibly by promoting lithium efflux from CSF due to increased NKCC1 expression in the choroid plexus.

    DOI: 10.1007/s11095-008-9612-5

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  • Frequency of decreased renal function between patients treated with brand and generic products of vancomycin hydrochloride injection Reviewed

    Yuki Izuwa, Satoshi Ueshima, Tomoaki Sato, Masatoshi Okazaki, Tetsuya Aiba, Hiromu Kawasaki, Yuji Kurosaki, Toshiaki Sendo

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN   128 ( 10 )   1493 - 1498   2008.10

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    The frequency of decreased renal function was compared between patients treated with brand and generic products of vancomycin injection (VCM) in a retrospective manner based on the clinical examination records archived in Okayama University Hospital. A total of 122 patients were found to have been solely treated with vancomycin injection for MRSA infection, and their examination records were analyzed. The renal function of those patients was evaluated based on the serum creatinine concentration (SCr), and patients whose SCr was maximally elevated above the defined upper limit of the normal range (1.20 mg/dl for mates and 0.96 mg/dl for females) were considered to show decreased renal function. Although the amount of VCM administered to patients was larger in the case of generic rather than brand products, the percentage of patients whose renal function was decreased during VCM treatment was not significantly different between the VCM products, in which 2 among 62 patients receiving the brand product and 4 among 60 receiving the generic product were reported to show decreased renal function. It was additionally revealed that 3 of those 4 patients with a decreased renal function related to the generic product were not treated as instructed by the package insert, and their trough VCM concentration exceeded the recommended level of 10 mu g/ml. With these findings, the brand and generic VCM products are considered to be similar regarding the adverse effect of decreasing renal function.

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  • 岡山大学薬学部におけるPBL導入の現状と6年制に向けての課題

    岡崎宏美, 四宮一昭, 名倉弘哲, 北村佳久, 合葉哲也, 高山房子, 黒崎勇二, 川崎博己, 千堂年昭

    医療薬学フォーラム講演要旨集   16th   304   2008.7

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  • ロバスト回帰を用いる難治性ネフローゼ患者におけるシクロスポリンのAUC推定方法に関する検討

    上島 智, 合葉 哲也, 佐藤 智昭, 黒崎 勇二, 瀧上 慶一, 杉山 斉, 槇野 博史, 千堂 年昭

    TDM研究   25 ( 3 )   s182 - s182   2008.6

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  • 塩酸バンコマイシンの先発医薬品と後発医薬品における腎障害発現状況の比較検討

    出羽 祐基, 上島 智, 佐藤 智昭, 岡崎 昌利, 合葉 哲也, 川崎 博己, 黒崎 勇二, 千堂 年昭

    日本薬学会年会要旨集   128年会 ( 4 )   168 - 168   2008.3

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  • Characterization of non-linear relationship between total and unbound serum concentrations of valproic acid in epileptic children Reviewed

    S. Ueshima, T. Aiba, T. Makita, S. Nishihara, Y. Kitamura, Y. Kurosaki, H. Kawasaki, T. Sendo, Y. Ohtsuka, Y. Gomita

    Journal of Clinical Pharmacy and Therapeutics   33 ( 1 )   31 - 38   2008.2

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    Objective: To establish a regression equation to properly estimate the unbound serum concentration of valproic acid (VPA) from its total serum concentration; the relationship between total and unbound serum VPA concentrations was retrospectively characterized.
    Methods: Data were obtained from the clinical examination records that were routinely archived during therapeutic drug monitoring. The screening encompassed 342 records of 108 paediatric patients whose total and unbound VPA concentrations had been determined. The relationship between total and unbound VPA concentrations was characterized according to the Langmuir equation by taking account of inter-individual variability with the NONMEM program.
    Results: The total VPA concentration (C-t) in the screened patients ranged from 5.5 to 179.8 mu g/mL, and the unbound VPA concentration (C-f) increased in a non-linear manner as the total VPA concentration increased. Taking account of the effects of antiepileptics concurrently administered, the VPA dissociation constant (K-d) and maximum binding site concentration (B-m) were 7.8 +/- 0.7 and 130 +/- 4.5 mu g/mL respectively, for the regression equation, C-t = C-f + B-m.C-f/(K-d + C-f). An alteration in the unbound concentration was seen in patients who were treated with the combination of VPA and ethosuximide and in those who received two additional antiepileptics.
    Conclusions: A regression equation for estimation of the unbound VPA concentration, based on total VPA concentration collected during routine therapeutic drug monitoring was established. Use of two additional antiepileptics and ethosuximide treatment was considered as potential factors affecting unbound VPA concentration.

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  • Individualized dosage adjustment of valproic acid based on unbound serum concentration in intractable epileptic children Reviewed

    Ueshima Satoshi, Aiba Tetsuya, Sato Tomoaki, Kawasaki Hiromu, Kurosaki Yuji, Ohtsuka Yoko, Sendo Toshiaki

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN   128   92   2008

  • Application of the correlation of in vitro dissolution behavior and in vivo plasma concentration profile (IVIVC) for soft-gel capsules - a pointless pursuit? Reviewed

    Hidekatsu Nishimura, Chlaki Hayashi, Tetsuya Aiba, Ichiro Okamoto, Yuji Miyamoto, Susumu Nakade, Kazuhisa Takeda, Yuji Kurosaki

    Biological and Pharmaceutical Bulletin   30 ( 11 )   2221 - 2225   2007.11

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    Plasma concentration profiles of arundic acid ((R)-(-)-2-propyloctanoic acid), an oil-like medicine, administered as soft-gel capsules in human clinical tests were predicted from the dissolution test data of the soft-gel capsules with different storage terms (short- and long-term stored drugs) by applying the in vitro-in vivo correlation (IVIVC). We established two linear-regression IVIVCs, which were characterized by either the in vitro dissolution behaviors against the pH 8.0 dissolution medium or the pH 6.8 dissolution medium containing 2% sodium dodecyl sulfate (SDS), in this study. Also, the prediction accuracies for the in vivo plasma profiles in humans for these two IVIVCs were compared. Regarding dissolution from the long-term stored capsule in pH 8.0 dissolution medium without surfactant, the prediction accuracies of the in vivo plasma profiles in humans were not satisfactory for the obtained IVIVC. The use of pH 6.8 dissolution medium containing 2% SDS, according to the Japanese guideline, improved the dissolution of the long-term stored capsule. Furthermore, the prediction accuracies for the in vivo plasma profiles in humans for these two IVIVCs were compared. The IVIVC established by the in vitro dissolution data obtained with the dissolution medium containing surfactant more effectively predicted the plasma drug concentration profiles following oral administrations of the soft-gel capsules under both storage conditions.

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  • 乳幼児における血中遊離形バルプロ酸濃度の遡及的解析

    合葉 哲也, 上島 智, 石川 七瀬, 佐藤 智昭, 川崎 博己, 黒崎 勇二, 大塚 頌子, 千堂 年昭

    臨床薬理   38 ( Suppl. )   S237 - S237   2007.11

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  • Evaluation of intramuscular lateral distribution profile of topically administered acetaminophen in rats Reviewed

    Yuji Kurosaki, Masahiro Tagawa, Akiho Omoto, Hiroshi Suito, Yukiko Komori, Hiromu Kawasaki, Tetsuya Aiba

    International Journal of Pharmacetics   343 ( 1-2 )   190 - 195   2007.10

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    To clarify to what extent topically administered drug molecules horizontally permeate into tissues surrounding the administration site, the intramuscular lateral concentration profile of acetaminophen was investigated in vivo using the microdialysis method in rats. When acetaminophen was intramuscularly administered for 6 h in a pinpoint manner at a constant rate of 3 mu g/min, it was clearly detected in the muscle surrounding the administration site, being 17.5 mu g/ml when measured at a 2 mm distance from the administration site. The concentration in the muscle was decreased as the distance increased, and those measured at 5 mm and 40 rum were 0.35 mu g/ml and 0.09 mu g/ml, respectively. In addition, it was shown that the concentration in the muscle at 40 turn reflected the compound's concentration in plasma, but not the compound's horizontal permeation from the administration site. With these observations, the intramuscular distribution profile of acetaminophen was numerically characterized according to Fick's law. As a result, it was revealed that horizontal permeation is the primary process accountable for the increased intramuscular concentration only in the area adjacent to the administration site, and the radius of the adjacent area was calculated to be 5.80 turn for acetaminophen. (C) 2007 Elsevier B.V. All rights reserved.

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  • てんかん患児における遊離形バルプロ酸濃度に及ぼす併用薬の影響

    上島 智, 合葉 哲也, 佐藤 智昭, 川崎 博己, 黒崎 勇二, 千堂 年昭

    TDM研究   24 ( 3 )   s153 - s153   2007.7

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  • Alteration of therapeutic efficacy of lipid microspheres incorporating prostaglandin E-1 by mixing with aqueous solution Reviewed

    Yukiko Komori, Tetsuya Aiba, Miki Kushima, Hiromu Kawasaki, Yuji Kurosaki

    Journal of Pharmaceutical Sciences   96 ( 4 )   935 - 943   2007.4

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    To clarify whether the therapeutic efficacy of lipid microspheres incorporating prostaglandin E-1 (lipo-PGE(1)) is altered when mixed and coinfused with clinical solutions, the original lipo-PGE(1) solution (20 mu g/mL) was mixed with three clinical infusion solutions: 0.9% sodium chloride solution, Hartmann's solution, and fat emulsion for parenteral nutrition. These diluted lipo-PGE(1) (2 mu g/mL) solutions were administered to rats, and their hemodynamic and antiplatelet effects were examined. Peripheral blood flow was increased by 76 +/- 4% from the control level when the lipo-PGE(1) solution diluted with the fat emulsion was administered, while it was increased by 43 +/- 6% and 36 +/- 17%, respectively, when the lipo-PGE(1) solutions diluted with 0.9% sodium chloride and Hartmann's solution were administered. As for the antiplatelet effects of the lipo-PGE(1) solutions, the progression of digit gangrene in thromboangiitis obliterans (TAO) rats was significantly suppressed by the administration of lipo-PGE(1) solution diluted with the fat emulsion, but it was not suppressed by lipo-PGE(1) solution diluted with 0.9% sodium chloride. These findings indicate that the therapeutic efficacy of lipo-PGE(1) is decreased when it is mixed with an aqueous solution such as 0.9% sodium chloride.

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  • Effects of capsaicin on intestinal cephalexin absorption in rats Reviewed

    Yukiko Komori, Tetsuya Aiba, Risa Sugiyama, Chie Nakai, Hiromu Kawasaki, Yuji Kurosaki

    Biological and Pharmaceutical Bulletin   30 ( 3 )   547 - 551   2007.3

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    The effects of capsaicin on intestinal cephalexin absorption were investigated by means of in situ single pass perfusion in rats to clarify whether this pungent compound present in spice is a potential factor altering the intestinal drug absorption processes. Under the control condition, cephalexin was absorbed at a rate of 1.16 +/- 0.08 and 0.90 +/- 0.06 nmol/min/cm in the jejunum and ileum, respectively. The intestinal cephalexin absorption rate was decreased when capsaicin was dissolved in the perfusate at a concentration of 400 mu m, being 0.54 +/- 0.07 and 0.46 +/- 0.10 nmol/min/cm in the jejunum and ileum, respectively. The inhibitive effect of capsaicin on intestical cephalexin absorption was diminished when ruthenium red, a non-selective inhibitor of the transient receptor potential (TRP) cation channels, was intravenously infused into the rat during the experiment. Moreover, when we evaluated the paracellular permeability of cephalexin by utilizing a competitive inhibitor, glycylsarcosine, it was demonstrated that glycylsarcosine-insensitive intestinal cephalexin absorption in the jejunum was increased by 4.5 times in the presence of 400 mu m capsaicin. These findings indicate that capsaicin affects both transcellular and paracellular pathways of intestinal cephalexin absorption by interacting with the I RP cation channels in intestinal tissues, in which capsaicin seems to change the transport activity of H+/peptide co-transporter 1 (PEPT1), and to a lesser degree, it seems to alter the paracellular permeability of the intestinal epithelia.

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  • Capsaicin-induced increase of intestinal cefazolin absorption in rats Reviewed

    Yukiko Komori, Tetsuya Aiba, Chie Nakai, Risa Sugiyama, Hiromu Kawasaki, Yuji Kurosaki

    Drug Metabolism and Pharmacokinetics   22 ( 6 )   445 - 449   2007

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    The effect of capsaicin on intestinal cefazolin absorption was examined by means of an in situ closed loop method in rats to clarify whether the vanilloid receptor (TRPV1) is involved in drug absorption driven by passive diffusion. In control experiments with 1 mg/mL cefazolin, the amount of cefazolin absorbed from the closed loop was 15.3 +/- 1.5 mu g/cm in the rat jejunum. The absorption amount was increased to 22.8 +/- 0.9 and 23.4 +/- 2.4 mu g/cm when capsaicin was applied with cefazolin at concentrations of 10 and 400 mu M, respectively. The enhancing effect of capsaicin on cefazolin absorption was suppressed when ruthenium red, a non-selective inhibitor of transient receptor potential (TRP) cation channels, was intravenously infused into the rat during the experiment. Cefazolin accumulation in the intestinal tissue was not altered in the presence of capsaicin. Collectively, the mechanism accounting for the capsaicin-induced increase in the intestinal cefazolin absorption is probably that capsaicin associating with TRPV1 increases the intrinsic permeability of cefazolin in intestine.

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  • Evaluation of diffusion controlled vesicle (DCV) system for oral extended release by the in-vivo dissolution behaviop and the resulting pharmacokinetic profiles

    Masanari Mabuchi, Kozo Tagawa, Tetsuya Aiba, Yuji Kurosaki

    Drug Meatbolism Reviews   39   270 - 270   2007

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  • 光に不安定な薬剤の簡易懸濁法を用いた投与方法について

    座間味 義人, 槙田 崇志, 安藤 哲信, 倉田 なおみ, 合葉 哲也, 黒崎 勇二, 天野 学, 名和 秀起, 北村 佳久, 千堂 年昭, 五味田 裕, 高山 房子, 川崎 博己

    日本医療薬学会年会講演要旨集   16   2006.9

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  • バルプロ酸TDMデータの遡及的解析

    槙田 崇志, 上島 智, 西原 茂樹, 合葉 哲也, 千堂 年昭, 川崎 博己, 五味田 裕, 黒崎 勇二

    日本医療薬学会年会講演要旨集   16   2006.9

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  • Peritoneal dialysis alters tolbutamide pharmacokinetics in rats with experimental acute renal failure Reviewed

    Tetsuya Aiba, Mizuki Horiuchi, Takashi Makita, Yukiko Komori, Hiromu Kawasaki, Yuji Kurosaki

    Drug Metabolism and Pharmacokinetics   21 ( 4 )   291 - 296   2006

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    The plasma concentration profile of the antidiabetic agent tolbutamide was investigated in glycerol-induced acute renal failure (ARF) rats receiving or not receiving peritoneal dialysis (PD) to assess the impact of performing dialysis on tolbutamide pharmacokinetics. It was revealed that the plasma concentration of tolbutamide was decreased by 23.4% by performing PD in ARF rats, while it was not changed by PD in normal rats. The decrease in the plasma concentration of tolbutamide was nearly proportional to the increase in its volume of distribution. To clarify the mechanisms responsible for the decreased tolbutamide concentration caused by PD, the plasma protein binding of tolbutamide was examined in normal and ARF rats. The plasma unbound fraction of tolbutamide was higher in ARF rats than in normal rats, and the dissociation constants were 3.5 +/- 0.7 and 5.5 +/- 0.2 mu g/mL in normal and ARF rats, respectively. These results indicated that the unbound fraction of tolbutamide was increased in ARF rats because of its protein binding being suppressed. It is therefore likely that since a measurable amount of tolbutamide can distribute in peritoneal dialysate in ARF rats, but not in normal rats, the plasma concentration of tolbutamide was decreased by performing PD only in ARF rats. These findings suggest that diabetes medication with tolbutamide should be carefully performed in patients receiving dialysis treatment.

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  • The effects of culture conditions on CYP3A4 and MDR1 mRNA induction by 1α,25- dihydroxyvitamin D3 in human intestinal cell lines, Caco-2 and LS180. Reviewed

    Aiba T, Susa M, Fukumori S, Hashimoto Y

    Drug Metabolism and Pharmacokinetics   20 ( 4 )   268 - 274   2005.8

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  • Evaluation of phenytoin dosage regimens based on genotyping of CYP2C subfamily in routinely treated Japanese patients. Reviewed

    Taguchi M, Hongou K, Yagi S, Miyawaki T, Takizawa M, Aiba T, Hashimoto Y

    Drug Metabolism and Pharmacokinetics   20 ( 2 )   107 - 116   2005.5

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  • Intestinal expression and metabolic activity of the CYP3A subfamily in female rats Reviewed

    T Aiba, M Yoshinaga, K Ishida, Y Takehara, Y Hashimoto

    Biological and Pharmaceutical Bulletin   28 ( 2 )   311 - 315   2005.2

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    The intestinal expression of the CYP3A subfamily was investigated in female rats, and the intestinal metabolism of two CYP3A substrates, testosterone and rifabutin, was examined and compared between males and females. CYP3A1/23 and CYP3A2 intestinal expression was barely detected in male and female rats. Although CYP3A9 was predominantly expressed in the female rat liver, its expression in the intestine was not different between the two sexes. The rate of testosterone 6beta-hydroxylation in the female intestine was similar to that for males. Rifabutin was also metabolized at similar rates in both intestines, although the metabolic rate was greater in the female liver. These results indicate that the intestinal drug metabolizing activity of the CYP3A subfamily is similar between males and females, and that CYP3A9 is involved in the intestinal metabolism of CYP3A substrates in both sexes.

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  • Pharmacokinetic characterization of transcellular transport and drug interaction of digoxin in Caco-2 cell monolayers Reviewed

    T Aiba, K Ishida, M Yoshinaga, M Okuno, Y Hashimoto

    Biological and Pharmaceutical Bulletin   28 ( 1 )   114 - 119   2005.1

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    To characterize the intestinal absorption of digoxin, its transcellular transport and drug interaction activity was investigated using Caco-2 cell monolayers. We examined digoxin transport in the presence and absence of ouabain to determine whether digoxin binding to Na+,K+-ATPase affects its transcellular digoxin transport, and evaluated its influx and efflux clearance by model-dependent pharmacokinetic analysis. Transcellular transport in the basal-to-apical direction was greater than that in the opposite direction. In addition, ouabain decreased the cellular accumulation of digoxin, but it did not alter its transcellular transport profile. The observations for transcellular transport and cellular accumulation in the presence of ouabain were used for the pharmacokinetic analysis, which showed that the efflux clearance of digoxin on the apical side of the monolayer was 15 times greater than that on the basal side. Apical-to-basal transport was increased by carvedilol and pimobendan, and these compounds suppressed the efflux clearance on the apical side and the influx clearance on the basal side. These findings indicate that the intestinal absorption of digoxin is primarily dominated by the efflux process on the luminal side of the intestine, and that carvedilol and pimobendan may vary the rate of intestinal digoxin absorption mainly by inhibiting its exsorptive transport.

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  • 小腸におけるCYP3A4発現調節活性の個体間変動因子の解明

    合葉哲也

    中冨健康科学振興財団第16回研究助成事業集   2005

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  • Caco-2細胞を用いた小腸の薬物吸収障壁機能の解析:ジゴキシン経細胞輸送と薬物相互作用メカニズムの速度論的評価

    合葉哲也, 田口雅登, 橋本征也

    臨床薬学の進歩   2005

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  • ビタミンD受容体によるCYP3A4発現誘導と生体防御のメカニズム

    合葉 哲也

    ファルマシア   39 ( 5 )   454 - 455   2003.5

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  • Effect of experimental renal dysfunction on bioavailability of ajmaline in rats Reviewed

    Hashimoto Y, Aiba T, Yasuhara M, Hori R

    Journal of Pharmacy and Pharmacology   53 ( 6 )   805 - 813   2001.6

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  • Single dose pharmacokinetics and pharmacodynamics of oxazepam in normal and renal dysfunction rats Reviewed

    Kalpana Srivastava, Tomomi Hatanaka, Tetsuya Aiba, Kazunori Katayama, Tamotsu Koizumi

    Biological and Pharmaceutical Bulletin   22 ( 6 )   627 - 632   1999

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    The purpose of this work was to investigate the disposition characteristics and pharmacodynamics of a benzodiazepine, oxazepam, in renal dysfunction rats. For the in vivo experiment, normal and renal dysfunction rats were given 40 mg/kg of oxazepam as the bolus dose. A quantitative electroencephalographic (EEG) method was used as the surrogate measure of the pharmacological response. The oxazepam concentration in plasma and cerebrospinal fluid (CSF) was assayed by the HPLC method. The steady-state volume of distribution and clearance based on total and unbound plasma did not change in renal dysfunction rats. Amplitude changes in the EEG induced by oxazepam in normal and renal dysfunction rats were characterized by a log- concentration response model or sigmoidal E(max) model. The pharmacodynamic parameters from these models were not altered in renal dysfunction. In in vitro binding studies for γ-aminobutyric acid (GABA)-benzodiazepine receptor complex, the oxazepam-induced effect was not potentiated by the plasma dialysate from renal dysfunction rats. Thus, it was suggested that the brain sensitivity to benzodiazepines was not altered in renal insufficiency.

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  • Effect of dosage form on stereoisomeric inversion of ibuprofen in volunteers Reviewed

    Tetsuya Aiba, Mary M. Tse, Emil T. Lin, Tamotsu Koizumi

    Biological and Pharmaceutical Bulletin   22 ( 6 )   616 - 622   1999

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    Twelve healthy volunteers were given ibuprofen racemate in two different dosage forms, a suspension and a tablet. The plasma concentration-time profiles of S- and R-ibuprofen were determined and the R-ibuprofen inversion clearance was calculated. Although the area under the curve was almost the same in both the suspension and tablet studies, the inversion clearance was larger in the suspension study than in the tablet study (1.18±0.65 and 0.72±0.63 l/h, shown as the mean±S.D.). The Michaelis-Menten parameters for this inversion process were then determined in vitro with human liver microsomes (1.3±0.2 mM for K(m) and 3.1±0.3 nmol/min/mg protein for V(max), shown as the mean±S.D.). These parameters indicated that the stereoisomeric inversion of R-ibuprofen in the liver was not likely to be saturated at the plasma concentrations measured in the volunteer study. The profile of the plasma concentration ratio between S-ibuprofen and R-ibuprofen revealed a difference in the early phase of these two studies. Therefore the inversion difference between those two studies probably resulted from the difference in the absorption phase of each dosage form. Our study demonstrated that R- ibuprofen inversion could be affected by alteration of dosage form.

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  • Application of a non-linear dispersion model to analysis of the renal handling of p-aminohippurate in isolated perfused rat kidney Reviewed

    Tetsuya Aiba, Shin Kubota, Tamotsu Koizumi

    Biological and Pharmaceutical Bulletin   22 ( 6 )   633 - 641   1999

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    To analyze the renal handling of therapeutic compounds observed as a non-linear process with a diffusion phenomenon, we employed a non-linear dispersion model described with a partial differential equation and solved it by using the finite difference method with an implicit scheme in a model dependent analysis. In this study, the renal handling of p-aminohippurate (PAH) was investigated in isolated perfused rat kidney, in which a 50 μl bolus of injection solution containing [3]PAH and [14C]inulin was administered rapidly into the renal artery. The venous outflows were then collected for 15 min with a fraction collector. The renal extraction ratio of PAH was decreased from 65% to 18% as the PAH concentration in the injection solution was increased from 2 μM to 10 mM. The PAH outflow profile changed as the extraction process became saturated. With the non-linear dispersion model, the Miehaelis-Menten parameters for the PAH extraction process were estimated by a model fitting calculation. The calculated values were 0.83 μmol/min/kidney for V(max) and 89 μM for K(m). It was demonstrated that the model dependent analysis with a non-linear dispersion model is a useful approach to characterize renal drug handling, and is probably applicable for examining other non-linear processes which involve a diffusion phenomenon.

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  • Effects of probenecid and cimetidine on the renal excretion of 3’-azido-3’-deoxy-thymidine in rats Reviewed

    Aiba T, Sakurai Y, Tsukada S, Koizumi T

    Journal of Pharmacology and Experimental Therapeutics, 272(1): 94-99   272 ( 1 )   94 - 99   1995.1

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  • Kinetic analysis of neuromuscular blockade I: Relationship between twitch depression and stimulation frequency after d-tubocurarine administration Reviewed

    Tajima T, Kaneko K, Hatanaka T, Aiba T, Katayama K, Koizumi T

    Biological and Pharmaceutical Bulletin   17 ( 8 )   1083 - 1088   1994.8

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  • Kinetic analysis of neuromuscular blockade II: Train-of-four fade induced by d-tubocurarine and α-bungarotoxin Reviewed

    Tajima T, Kato Y, Hatanaka T, Aiba T, Katayama K, Koizumi T

    Biological and Pharmaceutical Bulletin   17 ( 8 )   1089 - 1093   1994.8

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  • Renal handling of tobramycin in the isolated perfused rat kidney Reviewed

    Tetsuya Aiba, Yoshie Itoga, Hiromasa Shimizu, Yusuke Tanigawara, Ryohei Hori

    Journal of Pharmaceutical Sciences   83 ( 5 )   723 - 726   1994

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    The renal handling of tobramycin (TOB), an aminoglycoside antibiotic (AG), was studied using a single‐pass isolated perfused rat kidney with moment analysis. In the bolus administration study at tracer concentration (7.4 μM), 32% of the glomerular‐filtrated TOB remained in the lumen, but no TOB was found in the vein. This ratio of the luminal uptake was reduced in a dose‐dependent manner. Other aminoglycosides such as gentamicin inhibited this uptake, but tetraethylammonium and glucosamine had no effect. In addition, under the alkalinuria condition, TOB uptake was decreased to 67% of the control value. This indicated that TOB has mainly been taken into the renal epithelial cells from their luminal site and that this uptake process was saturable and specific for AGs which have more than one cationic group. The present findings should be helpful in developing a method to reduce the nephrotoxicity of AGs and to identify their toxicity mechanisms. Copyright © 1994 Wiley‐Liss, Inc., A Wiley Company

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  • Role of p-glycoprotein in renal tubular secretion of digoxin in the isolated perfused rat kidney Reviewed

    Hori R, Okamura N, Aiba T, Tanigawara Y

    Journal of Pharmacology and Experimental Therapeutics   266 ( 3 )   1620 - 16258520/   1993.3

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  • Effect of l-mentol on the permeation of indomethacin, mannitol and cortisone through excised hairless mouse skin Reviewed

    Katayama K, Takahashi O, Matsui R, Morigaki S, Aiba T, Kakemi M, Koizumi T

    Chemical and Pharmaceutical Bulletin   40 ( 11 )   3097 - 3099   1992.1

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  • Moment analysis of drug disposition in kidney. II: Urine pH‐dependent tubular secretion of tetraethylammonium in the isolated perfused rat kidney Reviewed

    Akira Kamiya, Yusuke Tanigawara, Yoshihiro Saito, Yoshie Hayashi, Tetsuya Aiba, Ken‐Ichi Inui, Ryohei Hori

    Journal of Pharmaceutical Sciences   79 ( 8 )   692 - 697   1990

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    Effects of urine pH on the renal tubular secretion of an organic cation (tetraethylammonium, TEA) and an organic anion (p‐aminohippurate, PAH) were investigated using the isolated erythrocyte‐perfused rat kidney. The method was based on a multiple indicator dilution experiment and noncompartmental moment analysis. Treatment with sodium bicarbonate and sodium dihydrogen phosphate increased and decreased urine pH, respectively, but affected neither the condition of the perfused kidney nor the renal handling of albumin and inulin. In TEA studies, the increase of urine pH prolonged the mean residence time in renal epithelial cells (T̄cell) and reduced the apparent secretion intrinsic clearance, but did not influence the volume of distribution in the kidney (Vddrug). The decrease of urine pH did not affect these kinetic parameters. By contrast, PAH secretion was constant against the change of urine pH. Since any change in the basolateral membrane transport is reflected in Vddrug, the net transport from blood to cells can be regarded as similar under these treatments. On the other hand, the prolonged T̄cell of TEA with the increased urine pH suggested a slow transport from cells to lumen across the brush‐border membranes. The present results coincide with the hypothetical mechanism that organic cations are secreted via an active transport system, coupled to the countertransport of H+ into cells. In conclusion, the present method is useful to separately evaluate the transmembrane transport across both sides of the renal epithelial cells in a morphologically intact kidney. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company

    DOI: 10.1002/jps.2600790809

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  • Moment analysis of drug disposition in kidney. III: Transport of p‐aminohippurate and tetraethylammonium in the perfused kidney isolated from uranyl nitrate‐induced acute renal failure rats Reviewed

    Yusuke Tanigawara, Yoshihiro Saito, Tetsuya Aiba, Kou Ohoka, Akira Kamiya, Ryohei Hori

    Journal of Pharmaceutical Sciences   79 ( 3 )   249 - 256   1990

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    A different manner of insufficiency of renal epithelial cell transport between the organic anion and cation, p‐aminohippurate and tetraethylammonium, respectively, was observed in the perfused kidney isolated from uranyl nitrate‐induced acute renal failure (ARF) rats. The single‐pass outflow pattern of the perfused kidney was analyzed by noncompartmental moment analysis. The active tubular secretion was impaired faster than the reduction of glomerular filtration, and the tetraethylammonium secretion decreased at an earlier stage of ARF than p‐aminohippurate. The apparent uptake rate constant from blood to cells of p‐aminohippurate was reduced with the progress of ARF and associated with the amount of this drug secreted, whereas the uptake rate constant of tetraethylammonium did not change until the late stage of ARF. The mean residence time in renal epithelial cells of tetraethylammonium was prolonged with reduction of the amount to be secreted, while that of p‐aminohippurate remained unchanged. Therefore, the uptake of p‐aminohippurate across the basolateral membranes decreased gradually, and the transport across the brush border membranes was still unchanged after uranyl nitrate treatment. On the other hand, the secretion of tetraethylammonium from cells to lumen was impaired at first, and then the uptake from blood to cells was impaired. These results suggest that impairment by uranyl nitrate‐induced ARF appears at the carrier‐mediated transport process of the epithelial cell membranes for both organic anions and cations. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company

    DOI: 10.1002/jps.2600790315

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  • Moment analysis of drug disposition in kidney: Transcellular transport kinetics of p‐Aminohippurate in the Isolated Perfused Rat Kidney Reviewed

    Ryohei Hori, Yusuke Tanigawara, Yoshihiro Saito, Yoshie Hayashi, Tetsuya Aiba, Katsuhiko Okumura, Akira Kamiya

    Journal of Pharmaceutical Sciences   77 ( 6 )   471 - 476   1988

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    The mean renal epithelial cell residence time, T̄cell, was defined as a model‐independent characteristic of the transcellular transport process in the isolated perfused kidney. The transcellular transport process includes transport at the basolateral membrane, diffusion in the cytosol, and transport at the brush border membrane. The parameter T̄cell represents the mean time for the drug secreted from the tubules to pass through the renal epithelial cells, and is calculated as the difference of the mean urinary transit time between secreted drug and inulin in the single‐pass perfusion system. Therefore, the urinary excretion rate–time course is indispensable to evaluate T̄cell. p‐Amino‐hippuric acid was used as a model compound. The bovine erythrocytes in the perfusate kept the isolated kidney in an almost constant physiological condition, including secretion function. The renal vein outflow curves were also analyzed by the use of moments. The dispersion in the catheter was corrected by a deconvolution. The apparent secretion intrinsic clearance and the apparent volume of distribution were calculated from the moments. The present method will be useful for analysis of the transcellular transport mechanism and the effect of disease states on renal transport of drugs. Copyright © 1988 Wiley‐Liss, Inc., A Wiley Company

    DOI: 10.1002/jps.2600770602

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Books

  • 個別化医療を目指した臨床薬物動態学1-基礎編(共著)

    廣川書店  2016  ( ISBN:9784567484909

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Presentations

  • Effects of culture conditions on CYP3A4 and MDR1 mRNA induction by 1a,25- dihydroxyvitamin D3 in human intestinal cell lines, Caco-2 and LS180.

    Aiba T, Susa M, Fukumori S, Hashimoto Y

    Drug Metabolism Reviews  2005 

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    Event date: 2005

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  • Contribution of the first pass intestinal elimination to low bioavailability of lidocaine in rats

    Aiba T, Kimura M, Nishina K, Koizumi T

    Millennial World Congress of Pharmaceutical Sciences  2000.4 

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    Event date: 2000.4

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  • Characterization of steveoisomeric inversion of ibaprofen and fenoprofer in rat liver microsomes.

    Aiba T, Tse MM, Lin ET, Koizumi T

    American Association of Pharmaceutical Scientists Annual Meeting and Exposition  1998.11 

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    Event date: 1998.11

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  • Mean residence time in organs in toxicokinetic studies

    Tanigawara Y, He Y-L, Aiba T, Yasuhara M, Hori R, Hirouchi Y, Nakagawa H, Kawahara Y, Okada R

    Journal of Pharmacobio-Dynamics  1990.2 

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    Event date: 1990.2

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  • 炎症病態に伴う⾎糖降下薬ナテグリニドの薬効変動の解析

    ⻄脇あかね、床治佳、神志那萌⼦、松本和也、合葉哲也

    日本薬学会 第140年会  2020.3 

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  • 急性腎不全に伴うフェノバルビタールの中枢抑制作⽤の薬⼒学的変動機構

    松本和也, 鈴木啓一郎, 脇あかね, 合葉哲也

    日本薬学会 第140年会  2020.3 

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  • 急性腎不全ラットにおける中枢神経系抑制薬の薬効増強メカニズムの検討

    松本和也, 鈴木啓一郎, 合葉哲也

    第58回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2019.11.9 

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  • 急性組織炎症病態における糖尿病治療薬ナテグリニドの体内動態と薬効解析

    神志那萌子, 西脇あかね, 鈴木啓一郎, 藤本和貴, 合葉哲也

    第28回日本医療薬学会年会  2018.11.24 

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  • 中枢神経抑制薬の麻酔作用に及ぼす末梢組織炎症の影響

    鈴木啓一郎, 岡田淳芳, 原啓介, 松本和也, 神志那萌子, 合葉哲也

    第28回日本医療薬学会年会  2018.11.23 

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  • 急性腎不全に伴う中枢神経系の薬物感受性の変動と電解質平衡調節機構の変動

    日本薬学会第138年会  2018 

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  • 急性局所炎症モデルラットにおける糖尿病治療薬ナテグリニドの体内動態の変動メカニズム

    日本薬学会第138年会  2018 

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  • 急性腎不全モデルラットにおけるフェノバルビタールの薬効変動機構の解明

    日本薬学会第137年会  2017 

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  • ビタミン剤の配合成分量に基づく類似性解析

    日本薬学会第137年会  2017 

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  • 一般向け消炎鎮痛貼付製剤の俯瞰的特性評価

    日本薬学会第137年会  2017 

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  • バルプロ酸のTDMとその応用

    日本TDM学会第47回セミナー  2016 

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  • 急性腎不全ラットにおける中枢神経系作用薬の薬効変動メカニズム

    第55回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2016 

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  • 一般用医薬品の消炎鎮貼付剤の類似性評価

    第55回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2016 

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  • An increased hepatic drug metabolizing activity accompanied with experimentally induced lung impairment and hypoxemia in rats

    第30回日本薬物動態学会  2015 

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  • 急性腎不全ラットにおける肝臓の薬物代謝酵素の発現調節機構の変調

    日本薬学会第135年会  2015 

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  • Alteration of the pharmacological effects of the CNS-acting compounds in rats with acute renal failure

    第30回日本薬物動態学会  2015 

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  • Acute renal failure alters the induced mRNA expression of hepatic CYP3A subfamily in rats

    19th North American ISSX / 29th JSSX Joint Meeting  2014 

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  • Altered hepatic drug metabolizing activity in rats with acute lung impairment

    第19回北米薬物動態学会・第29回日本薬物動態学会合同年会  2014 

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  • Acute renal failure alters the induced mRNA expression of hepatic CYP3A subfamily in rats

    第19回北米薬物動態学会・第29回日本薬物動態学会合同年会  2014 

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  • ラット肝薬物代謝酵素の発現誘導に及ぼす急性腎不全の影響

    第53回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2014 

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  • Altered pharmacological potency of the CNS-acting compounds in rats with acute renal failure

    第19回北米薬物動態学会・第29回日本薬物動態学会合同年会  2014 

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  • 急性肺機能障害ラットにおける肝薬物代謝の活性変動

    日本薬学会第134年会  2014 

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  • 急性腎不全ラットにおける中枢神経系作用薬の薬効変動機構

    日本薬学会第134年会  2014 

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  • Altered pharmacological potency of the CNS-acting compounds in rats with acute renal failure

    19th North American ISSX / 29th JSSX Joint Meeting  2014 

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  • Altered hepatic drug metabolizing activity in rats with acute lung impairment

    19th North American ISSX / 29th JSSX Joint Meeting  2014 

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  • Evaluation of the pharmacodynamics of CNS-acting compounds in rats with acute renal failure

    2013 

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  • 遊離形薬物濃度モニタに基づく筋肉内局所利用率の評価:局所冷却時の in vivo 拡散モデルによる数理的解析

    日本薬剤学会第28年会  2013 

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  • 急性局所炎症に伴う薬物肝代謝活性の変動メカニズムの検討

    日本薬学会第133年会  2013 

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  • 肝ラット肝薬物代謝活性に及ぼす肺障害の影響

    第52回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2013 

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  • 双極性障害患者に対するラモトリギンの使用実態調査と考察

    第23回日本医療薬学会年会  2013 

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  • Effects of lung impairment on the hepatic drug metabolizing activity in rats

    第28回日本薬物動態学会年会  2013 

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  • Evaluation of the pharmacodynamics of CNS-acting compounds in rats with acute renal failure

    第28回日本薬物動態学会年会  2013 

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  • Effects of lung impairment on the hepatic drug metabolizing activity in rats

    2013 

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  • Microdialysis 法を用いた薬物の筋肉内局所動態評価:局所冷却による局所薬物利用率の増大

    第28回日本DDS学会学術集会  2012 

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  • 湿潤療法用被覆型外用基剤としてのL-HPC含水ゲルシートの製剤的特性評価

    日本薬剤学会第27年会  2012 

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  • ラット肝CYP3A代謝活性に及ぼす急性局所炎症の影響

    第51回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2012 

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  • JPALS/CL6ジェネラリストに期待すること

    第45回日本薬剤師会学術大会  2012 

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  • Effect of intraperitoneal lipid emulsions on plasma-to-peritoneal transfer of lipophilic drugs in rats

    第27回日本薬物動態学会年会  2012 

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  • 腹腔内に注入した脂肪乳剤が血漿中及び腹腔内薬物動態に及ぼす影響:脂溶性の異なる薬物での比較検討

    第51回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2012 

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  • Evaluation of dynamic diffusion process for developing focally acting DDSs: Improvement of focal bioavailability by topical cooling

    第6回次世代を担う若手医療薬科学シンポジウム  2012 

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  • Effects of acute local inflammation on the hepatic expressions of CYP3A subfamily in rats

    第27回日本薬物動態学会年会  2012 

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  • ラットにおけるキトサンを用いた難吸収性抗ウイルス薬の消化管吸収改善

    日本薬剤学会第27年会  2012 

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  • ラット脳脊髄液の電解質平衡調節機構に及ぼす急性炎症の影響

    日本薬学会第132年会  2012 

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  • 脂肪乳剤微小透析法(Lipo-MD法)による親油性薬物の局所動態モニタ特性の改善

    日本薬剤学会第27年会  2012 

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  • ベットサイドの臨床薬理-移植と免疫抑制剤

    第33回日本臨床薬理学会学術総会  2012 

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  • Evaluation of dynamic diffusion process for developing focally acting DDSs: Improvement of focal bioavailability by topical cooling

    2012 

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  • Effects of acute local inflammation on the hepatic expressions of CYP3A subfamily in rats

    2012 

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  • Effect of intraperitoneal lipid emulsions on plasma-to-peritoneal transfer of lipophilic drugs in rats

    2012 

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  • 新規RXRアゴニスト及びその類縁化合物のヒト肝における代謝特性の予測

    日本薬学会第132年会  2012 

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  • 急性炎症に伴う電解質の脳脊髄液移行特性の変動評価

    第50回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2011 

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  • Effect of acute inflammation on lithium disposition to cerebrospinal fluid in rats

    2011 

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  • Metabolic properties of novel retinoid X receptor agonists possessing various side chain structures in liver microsomes

    2011 

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  • ラットにおける薬物肝代謝酵素の発現に及ぼす急性腎不全の影響

    日本薬学会第131年会  2011 

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  • Studies on the biopharmaceutical characteristics of novel PPAR pan-agonist, TIPP-703, and its pharmaceutical modification to improve intestinal absorption

    2011 

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  • 薬物の筋肉内拡散・ 分布動態に及ぼす血流量の影響:局所冷却時の動態特性

    日本薬剤学会第26年会  2011 

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  • ラットにおけるキトサンのアシクロビル消化管吸収促進機構の検討

    日本薬学会第131年会  2011 

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  • Effect of acute inflammation on lithium disposition to cerebrospinal fluid in rats

    第26回日本薬物動態学会年会  2011 

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  • 肺移植患者におけるシクロスポリン経口クリアランスに及ぼす移植後経過日数の影響

    第32回日本臨床薬理学会年会  2011 

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  • Studies on the biopharmaceutical characteristics of novel PPAR pan-agonist, TIPP-703, and its pharmaceutical modification to improve intestinal absorption

    第26回日本薬物動態学会年会  2011 

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  • 新規骨格を有するRXRアゴニストの側鎖構造と肝代謝活性の相関解析

    第50回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2011 

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  • 肺移植患者におけるタクロリムス血中濃度推移の母集団解析

    第28回日本TDM学会・学術大会  2011 

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  • Metabolic properties of novel retinoid X receptor agonists possessing various side chain structures in liver microsomes

    第26回日本薬物動態学会年会  2011 

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  • 新規骨格を有するRXRアゴニストの体内動態に関する基礎的検討

    日本薬学会第130年会  2010 

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  • 脂肪乳剤を用いた腹膜透析が脂溶性薬物の血漿中濃度推移に及ぼす影響

    第49回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2010 

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  • In vivoにおけるキトサンのアシクロビル吸収促進機構の検討

    第49回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2010 

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  • ラットにおける薬物肝代謝活性に及ぼす急性腎不全の影響

    第49回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2010 

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  • 脂肪乳剤を用いた微小透析法(Lipo-MD法):薬物の脂溶性が透析特性に及ぼす影響

    第49回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2010 

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  • キトサンによるアシクロビルの消化管吸収促進に関する検討

    第20回日本医療薬学会年会  2010 

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  • Microdialysis study in evaluation of intramuscular lateral distribution profiles of topically administered drugs in rats

    2010 

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  • In vivo における難吸収性抗ウイルス薬のバイオアベイラビリティ改善の試み

    日本薬剤学会第25年会  2010 

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  • 小児におけるテイコプラニンの母集団薬物動態解析 -血中濃度に及ぼす基礎疾患の影響-

    第27回日本TDM学会・学術大会  2010 

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  • L-HPC 含水ゲルシートの調整と被覆型外用基剤としての製剤学的特性評価

    日本薬剤学会第25年会  2010 

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  • Altered drug metabolizing activity of hepatic CYP3A subfamily in rats with acute renal failure

    第25回日本薬物動態学会年会  2010 

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  • Microdialysis study in evaluation of intramuscular lateral distribution profiles of topically administered drugs in rats

    第25回日本薬物動態学会年会  2010 

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  • 簡易懸濁用容器「けんだくん」を用いた光に不安定な薬剤の含量減少の抑制について

    日本薬学会第130年会  2010 

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  • Altered drug metabolizing activity of hepatic CYP3A subfamily in rats with acute renal failure

    2010 

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  • 血管平滑筋弛緩作用の薬力学モデル解析

    日本薬学会第130年会  2010 

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  • 急性腎不全ラットにおける薬物肝代謝活性の変動評価

    日本薬学会第130年会  2010 

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  • 脈絡叢におけるCSF電解質濃度の調節機構の in vivo 評価

    日本薬学会第130年会  2010 

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  • 新規レチノイドX受容体アゴニストNEt-3IPのラットにおける体内動態評価

    日本薬学会第129年会  2009 

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  • Pharmacokinetic characterization of novel retinoid X receptor agonists in rats

    第24回日本薬物動態学会年会  2009 

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  • Functional investigation of mechanisms responsible for lithium disposition to cerebrospinal fluid in rats

    第24回日本薬物動態学会年会  2009 

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  • 乳児を対象としたバルプロ酸血中遊離型濃度の母集団解析

    第30回日本臨床薬理学会年会  2009 

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  • ヨード造影剤との相互作用を有する薬剤に対するリスクマネージメント

    第19回日本医療薬学会年会  2009 

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  • MRSA感染症患者における塩酸バンコマイシン注射剤の腎毒性発現状況―ブランド医薬品とジェネリック医薬品の比較検討―

    第26回中国地区インフェクションフォーラム  2009 

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  • 新規レキシノイドのラットにおける体内動態特性の比較

    第48回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2009 

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  • アルベカシンの血中濃度モニタリングにおける腎機能マーカーシスタチンCの有用性評価

    第19回日本医療薬学会年会  2009 

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  • 脂肪乳剤を用いた微小透析法(Lipo- MD法)の透析特性:濃度変化に対する追随性の従来法との比較

    第48回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2009 

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  • 脈絡叢におけるリチウム輸送機構の in vivo 解析

    第48回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2009 

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  • Individualized dosage adjustment of valproic acid based on the prediction of its unbound serum concentration in epileptic infants

    第3回次世代を担う若手医療薬科学シンポジウム  2009 

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  • 急性腎不全における抗精神病薬リチウムの脳脊髄液移行動態に及ぼす性差の影響

    日本薬学会第129年会  2009 

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  • 乳児を対象としたバルプロ酸血中遊離型濃度の高精度推定式の構築

    第26回日本TDM学会・学術大会  2009 

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  • 脂肪乳剤を用いたマイクロダイアリシス法(Lipo-MD法)の局所薬物動態評価への応用

    日本薬剤学会第24年会  2009 

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  • Individualized dosage adjustment of valproic acid based on the prediction of its unbound serum concentration in epileptic infants

    2009 

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  • 118. Pharmacokinetic characterization of novel retinoid X receptor agonists in rats

    2009 

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  • Functional investigation of mechanisms responsible for lithium disposition to cerebrospinal fluid in rats

    2009 

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  • シスタチンCによる腎機能評価に基づくバンコマイシン血中濃度推移の母集団解析

    第47回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2008 

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  • 実験的急性腎不全ラットにおける肝代謝型塩基性薬物キニジンの体内動態変動因子の検討

    第47回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2008 

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  • 急性腎不全ラットにおけるリチウムの脳脊髄液移行動態の変動機構の検討

    第47回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2008 

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  • 微小透析法を用いた薬物の局所動態評価:フェニレフリンの筋肉内拡散動態と局所血流変化

    第47回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2008 

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  • ケトプロフェン貼付剤適用時の光分解物の生成に及ぼす抗酸化物質の効果

    第47回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2008 

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  • 塩酸バンコマイシンの先発医薬品と後発医薬品における腎障害発現状況の比較検討

    日本薬学会第128年会  2008 

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  • Choroid plexusにおける脳脊髄液の恒常性維持機構に及ぼす急性腎不全の影響

    日本薬学会第128年会  2008 

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  • 微小透析を用いた薬物の筋肉組織内拡散過程の評価

    日本薬剤学会第23年会  2008 

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  • 光に不安定な薬剤の簡易懸濁法を用いた経管投与方法について

    日本薬学会第128年会  2008 

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  • 作用発現動態の速度論的解析に基づく作用機構の考察:カルシウム拮抗薬による血管弛緩反応

    第113回日本薬理学会近畿部会  2008 

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  • 急性腎不全ラットにおける塩基性薬物キニジンの体内動態の変動

    第18回日本医療薬学会年会  2008 

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  • 乳幼児の発育に伴う遊離形バルプロ酸濃度の変動性評価

    第79回岡山小児てんかん懇話会  2008 

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  • 生涯学習の評価とは

    第41回日本薬剤師会学術大会  2008 

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  • 急性腎不全に伴うリチウムの脳脊髄液移行性の変動に対する性差の影響

    第18回日本医療薬学会年会  2008 

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  • 難治性ネフローゼ症候群患者におけるシクロスポリン血中濃度推移の母集団解析

    第47回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2008 

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  • Suppressing effect of antioxidants on the photodegradation of transdermally applied ketoprofen with UV-exposure

    第23回日本薬物動態学会年会  2008 

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  • シスプラチン投与時における水分負荷と腎障害発現頻度の実態調査

    第16回クリニカルファーマシー・シンポジウム  2008 

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  • ロバスト回帰を用いる難治性ネフローゼ患者におけるシクロスポリンのAUC 推定方法に関する検討

    第25回日本TDM学会・学術大会  2008 

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  • 岡山大学薬学部におけるPBL導入の現状と6年制に向けての課題

    第16回クリニカルファーマシー・シンポジウム  2008 

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  • 大学病院における緩和ケア〜緩和ケアチームでの薬剤師の役割〜

    第16回クリニカルファーマシー・シンポジウム  2008 

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  • Individual dosage adjustment of valproic acid based on unbound serum concentration in intractable epileptic children.

    第2回次世代を担う若手医療薬科学シンポジウム  2008 

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  • 乳幼児における血中遊離形パルプロ酸濃度の遡及的解析

    第28回日本臨床薬理学会年会  2007 

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  • 低置換度ヒドロキシプロピルセルロース(L-HPC)含水ゲルシートの調製と外用基剤としての特性評価

    第46回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2007 

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  • 脈絡叢の電解質輸送機構に及ぼす腎不全の影響

    第46回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2007 

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  • 各種L型Ca拮抗薬による血管弛緩作用動態の速度論的解析

    第46回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2007 

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  • 経皮吸収型ケトプロフェン製剤適用時の光分解物の生成に及ぼすアスコルビン酸誘導体の効果

    第46回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2007 

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  • 薬物の腸管吸収におけるバニロイド受容体による生理的制御

    日本薬剤学会第22年会  2007 

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  • Involvement of vanilloid receptor, TRPV1, in the physiological control of intestinal drug absorption in rats.

    3rd Pharmaceutical Sciences World Congress, Amsterdam, Netherlands  2007 

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  • てんかん患児における遊離型バルプロ酸濃度に及ぼす併用薬の影響

    第77回岡山小児てんかん懇話会  2007 

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  • てんかん患児における遊離形バルプロ酸濃度に及ぼす併用薬の影響

    第24回日本TDM学会・学術大会  2007 

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  • 職場の「余剰薬剤師」とならないために

    第40回日本薬剤師会学術大会  2007 

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  • 実務実習モデル・コアカリキュラムのトライアル(第5報)-多施設での実習時における学生の学習意欲向上のための教員の関与-

    第17回日本医療薬学会年会  2007 

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  • 乳幼児の発育に伴う血中遊離形バルプロ酸濃度の変動評価

    第46回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2007 

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  • Evaluation of diffusion controlled vesicle (DCV) system for oral extended release by the in-vivo dissolution behavior and the resulting pharmacokinetic profiles.

    8th International ISSX Meeting  2007 

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  • 抗躁薬リチウムの脳脊髄液移行性におよぼす腎不全の影響

    日本薬学会第127年会  2007 

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  • トルブタミドの腹膜透析性に及ぼすサルファ剤の影響

    第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2006 

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  • 光に不安定な薬剤の簡易懸濁法を用いた投与法について

    第16回日本医療薬学会年会  2006 

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  • バニロイド受容体刺激が消化管からの薬物吸収に及ぼす影響(Ⅱ)

    第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2006 

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  • マイクロダイアリシス法による抗躁薬リチウムの脳移行動態とその変動性の解析

    第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2006 

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  • 先発医薬品と後発医薬品のin vitro溶出動態の比較:塩酸ジルチアゼム製剤

    第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2006 

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  • Ketoprofenの皮膚内局所動態に及ぼす光照射の影響:微小透析法による検討

    第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2006 

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  • Effect of sulfonamides on pharmacokinetics of tolbutamide in rats receiving peritoneal dialysis

    第21回日本薬物動態学会年会  2006 

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  • 薬効動態のモーメント解析に基づく作用機構の考察:NOを介した血管弛緩反応

    第110回日本薬理学会近畿支部会  2006 

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  • バルプロ酸TDMデータの遡及的解析

    第16回日本医療薬学会年会  2006 

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  • ソフトカプセル剤の剤形変更後の血漿中薬物濃度推移予測の試み

    日本薬剤学会第21年会  2006 

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  • 微小透析法を用いた筋肉内における薬物拡散過程に関する研究

    日本薬剤学会第21年会  2006 

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  • Comparison of in vitro dissolution profiles of generic diltiazem formulations with innovator ones aimed to develop an in vitro–in vivo correlation (IVIVC)

    第21回日本薬物動態学会年会  2006 

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  • Effect of UV-irradiation on dermal pharmacokinetics of ketoprofen and its photoproducts in guinea pigs

    第21回日本薬物動態学会年会  2006 

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  • バルプロ酸血中濃度と併用薬、臨床検査値との関連性

    第74回岡山小児てんかん懇話会  2006 

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  • Rational clinical use for DDSs: Effects of dilution of Lipo-PEG1 injection with aqueous infusions on its therapeutic aspect in rats.

    13th NA ISSX / 20th JSSX Joint Meeting  2005 

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  • Effects of culture conditions on CYP3A4 and MDR1 mRNA induction by 1a,25-dihydroxyvitamin D3 in human intestinal cell lines, Caco-2 and LS180.

    13th NA ISSX / 20th JSSX Joint Meeting  2005 

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  • バニロイド受容体刺激が消化管からの薬物吸収に及ぼす影響

    第44回日本薬学会中四国支部学術大会  2005 

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  • A kinetic approach to bradykinin-induced vascular responses by the moment analysis.

    13th NA ISSX / 20th JSSX Joint Meeting  2005 

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  • 血管弛緩作用動態のモーメント解析に基づく作用機構の考察

    第44回日本薬学会中四国支部学術大会  2005 

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  • 微小透析法を用いた筋肉内投与された薬物の側方拡散に関する研究

    第44回日本薬学会中四国支部学術大会  2005 

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  • 薬物作用動態のモーメント解析に基づく作用機構解析の試み:血管作用薬

    第4回創薬・薬理フォーラム岡山  2005 

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  • Caco-2細胞におけるジゴキシン経細胞輸送の速度論的解析

    日本薬学会北陸支部第112回例会  2005 

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