Ohtani, Hisakazu

写真a

Affiliation

School of Medicine, Department of Clinical Pharmacy Division of Clinical Pharmacokinetics (Shinanomachi)

Position

Professor

External Links

Message from the Faculty Member 【 Display / hide

  • 医療薬学や臨床薬物動態学の楽しさを知っていただければと思います。

Profile Summary 【 Display / hide

  • 物理薬剤学や生物薬剤学、生化学、薬理学といった基礎薬学から、ヒトにおける臨床試験、患者や医療従事者を対象とした調査、疫学的調査、 医薬品情報、ファーマコメトリクス、IT技術にいたるさまざまな薬学領域の研究手法を活用することにより、おもに市販後の医薬品に関して、臨床的な問題点を解明し、適正かつ有効に使用するための 情報をつくるための研究を行っています。 具体的には、以下のような領域の研究を展開しています。 (1) 薬物の代謝過程やそこでの薬物相互作用の解析とテーラーメード医療への応用 (2) 消化管吸収過程における薬物相互作用の定量的予測 (3) 副作用軽減を目指した投与設計のための in vivo薬物動態・動力学的研究 (4) IT技術やファーマコメトリクスの活用による薬物治療の最適化

Career 【 Display / hide

  • 1994.04
    -
    1999.01

    Research Associate, Pharmacist, The University of Tokyo Hospital

  • 1999.01
    -
    1999.10

    Ohtani Estate Co., Ltd.

  • 1999.11
    -
    2005.03

    Associate Professor, Graduate School of Pharmaceutical Sciences, Kyushu University

  • 2005.04
    -
    2009.03

    Associate Professor, Graduate School of Pharmaceutical Sciences, The University of Tokyo

  • 2008.04
    -
    2009.03

    Adjunct Associate Professor, Graduate School of Interdisciplinary Information Studies The University of Tokyo

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Academic Background 【 Display / hide

  • 1986.04
    -
    1990.03

    The University of Tokyo, Faculty of Pharmaceutical Science, 薬学科

    University, Graduated

  • 1990.04
    -
    1992.03

    The University of Tokyo, Graduate School of Pharmaceutical Sciences

    Graduate School, Completed, Master's course

Academic Degrees 【 Display / hide

  • 博士 (薬学) Ph.D. (Pharmacy), The University of Tokyo, Dissertation, 1999.05

Licenses and Qualifications 【 Display / hide

  • Pharmacist, 1990.05

  • JSPHCS-Certified Pharmacist, 2003.01

  • Certified National Tour Guide-Interpreter (English), 2016.02

  • 第一種放射線取扱主任者, (2010/10/28 試験合格), 2018.06

  • Hazardous Materials Engineer (Class A), 1990.07

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Research Areas 【 Display / hide

  • Medical pharmacy (Clinical Pharmaceutical Science)

  • Applied pharmacology (Applied Pharmacology)

Research Keywords 【 Display / hide

  • pharmacometrics

  • personalized medication

  • interindividual variation of pharmacokinetics

  • drug interactions

 

Books 【 Display / hide

  • The Manga Guide to Pharmacokinetics

    OHTANI Hisakazu, Ohmusha, Co., Ltd., 2021.05,  Page: 181

  • 臨床検査データブック 2017-2018.

    高久 史麿(監修), 黒川 清, 春日 雅人, 北村 聖(編集), 大谷 壽一 ほか 執筆., 医学書院, 東京, 2017.01

  • 解消!ポリファーマシー 上手なくすりの減らし方

    OHTANI Hisakazu, じほう, 2016.08

    Scope: pp 219-243

  • MRテキストI, 医薬品情報2012 (2015年改訂)

    大谷壽一, 岡淳一郎, 折井孝男(編), 大谷壽一, 秋好健志, 他執筆., 南山堂, 東京, 2015

    Scope: 80-129

  • これだけは気をつけたい 高齢者への薬剤処方

    今井博久, 福島紀子 (編), 大谷 壽一ほか分担執筆, 医学書院, 2014.04

    Scope: pp 20-31

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Papers 【 Display / hide

  • Novel method to estimate the appropriate dosing interval for activated charcoal to avoid interaction with other drugs

    Ohtani H., Nakamura K., Imaoka A., Akiyoshi T.

    European Journal of Clinical Pharmacology (European Journal of Clinical Pharmacology)  76 ( 11 ) 1529 - 1536 2020.11

    Research paper (scientific journal), Accepted,  ISSN  00316970

     View Summary

    © 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Activated charcoal is known to adsorb a variety of drugs concomitantly administered and reduce their intestinal absorption, and separating the dosing is considered a practical approach to avoid this drug interaction. The aim of the present study was to develop and validate a simple method to estimate the sufficient dosing interval to avoid drug interaction using the pharmacokinetic profile of the subject drugs administered alone and the amplitude of interaction upon simultaneous administration with activated charcoal. Methods: For each subject drug, the pharmacokinetic profile and the amplitude of interaction, as assessed by AUCR (the ratio of area under the plasma concentration-time curve (AUC) in the presence of activated charcoal to that in its absence), were collected from previous reports. The AUCR value was estimated based on the compartment model under the assumption that the subject drug in the first gastrointestinal compartment is immediately adsorbed to a certain extent upon the administration of activated charcoal. The estimated AUCR (AUCRe) for each drug with certain dosing interval was compared with the respective AUCR value reported previously (AUCRobs). Results: Among twenty concentration profiles for 14 subject drugs obtained from previous reports, 15 AUCRe values fell in the range of 80–120% of the respective AUCRobs values. Conclusion: The developed method enabled estimation of the amplitude of DDI by activated charcoal administered in a certain dosing interval, whereas overestimation of AUCRe was observed for drugs that undergo extensive enterohepatic circulation.

  • Profile of the inhibitory effects of gefitinib in CYP2D6 variants in vitro

    Semba Y., Akiyoshi T., Hibino H., Imaoka A., Ohtani H.

    International Journal of Clinical Pharmacology and Therapeutics (International Journal of Clinical Pharmacology and Therapeutics)  58 ( 10 ) 539 - 542 2020.10

    Research paper (scientific journal), Accepted,  ISSN  09461965

     View Summary

    © 2020 Dustri-Verlag Dr. K. Feistle. Objective: CYP2D6 is a highly polymorphic metabolic enzyme with more than 100 genetic variants, some of which are associated with significantly altered enzyme activity, such as CYP2D6.2 (Arg296Cys, Ser486Thr), CYP2D6.10 (Pro34Ser, Ser486Thr), and CYP2D6.39 (Ser486Thr). Gefitinib is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) and is used to treat non-small-cell lung cancer with EGFR mutations. Gefitinib is known to competitively inhibit CYP2D6 activity. The aim of this study was to quantitatively compare the inhibitory effects of gefitinib on CYP2D6 enzyme kinetics among CYP2D6 variants. Materials and methods: The enzymatic activity of several CYP2D6 genetic variants; i.e., CYP2D6.1 (wild type), CYP2D6.2, CYP2D6.10, and CYP2D6.39, was assessed by examining the O-demethylation of dextromethorphan. Results and conclusion: The intrinsic clearance of dextromethorphan (Vmax/Km) for CYP2D6.2, CYP2D6.10, and CYP2D6.39 were 0.565-, 0.0376-, and 0.470-fold of that for wild type, respectively. For all variants, the mixed inhibition model was better at explaining the nature of the inhibitory effects of gefitinib than the competitive inhibition model. However, the inhibitory potency of gefitinib varied among the CYP2D6 genetic variants. The Ki values for CYP2D6.2, CYP2D6.10, and CYP2D6.39 were 1.4-, 2.5- and 1.5-fold higher than that for wild type, respectively, implying that these variants are less susceptible to the inhibition by gefitinib. The genetic variations in CYP2D6 might be one of the factors responsible for inter-individual differences in the strength of CYP2D6-mediated drug interactions involving gefitinib.

  • pH-dependent transport kinetics of the human organic anion-transporting polypeptide 1A2

    T. Morita, T Akiyoshi, R. Sato, K. Katayama, K. Yajima, H. Kataoka, A. Imaoka, Y. Sugimoto, H. Ohtani

    Drug Metabolism and Pharmacokinetics (Drug Metabolism and Pharmacokinetics)  35 ( 2 ) 220 - 227 2020

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  13474367

     View Summary

    © 2019 The Japanese Society for the Study of Xenobiotics Organic anion-transporting polypeptide (OATP) 1A2 is expressed on the apical sides of intestinal and renal epithelial cells and considered to be involved in the intestinal absorption and renal reabsorption of drugs. Although the transport activity of OATP1A2 is considered to be pH-dependent, the effects of pH on its kinetic parameters and on the potency of OATP1A2 inhibitors are yet to be elucidated. Some OATP are known to have multiple binding sites (MBS), but it remains unclear whether OATP1A2 has MBS. In the present study, we evaluated the influence of pH on the OATP1A2-mediated uptake of estrone 3-sulfate using OATP1A2-expressing HEK293 cells. The uptake of 0.3 μM estrone 3-sulfate by HEK293-OATP1A2 cells was pH-dependent. OATP1A2 exhibited bimodal saturation kinetics at pH 6.3 and 7.4. Compared with that seen at pH 6.3 (5.62 μM), the Km value of the high-affinity site was 8-fold higher at pH 7.4 (43.2 μM). In addition, the influence of pH on the potency of inhibitors varied among the examined inhibitors. These results suggest that the transport properties of OATP1A2 under lower pH conditions, such as those found in the microenvironments of the small intestinal mucosa and distal tubules, differ from those seen under neutral pH conditions.

  • Exacerbation of atrioventricular block associated with concomitant use of amlodipine and aprepitant in a lung cancer patient

    Hibino H, Makino Y, Sakiyama N, Makihara-Ando R, Hashimoto H, Akiyoshi T, Imaoka A, Fujiwara Y, Ohe Y, Yamaguchi M, Ohtani H

    International Journal of Clinical Pharmacology and Therapeutics    in press 2020

    Research paper (scientific journal), Accepted

  • 医薬品の第三者への転売・譲渡の違法性に関する消費者の意識調査

    大谷壽一, 藤井萌未, 今岡鮎子, 望月真弓, 山浦克典, 秋好健志

    医薬品情報学 22 ( 1 ) 30 - 34 2020

    Research paper (scientific journal), Joint Work, Accepted

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • Correction to: Novel method to estimate the appropriate dosing interval for activated charcoal to avoid interaction with other drugs (European Journal of Clinical Pharmacology, (2020), 76, 11, (1529-1536), 10.1007/s00228-020-02931-y)

    Ohtani H., Nakamura K., Imaoka A., Akiyoshi T.

    European Journal of Clinical Pharmacology (European Journal of Clinical Pharmacology)  76 ( 11 )  2020.11

    ISSN  00316970

     View Summary

    © 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Figure 3 image was inadvertently removed from the original article. The original article has been corrected.

  • 吸収過程のDDIについては、併用のタイミングをずらせば問題ないですか?

    大谷 壽一

    薬局 (南山堂)  67 ( 8 ) 2463 - 2468 2016.07

    Introduction and explanation (commerce magazine), Single Work,  ISSN  0044-0035

  • 外用剤(吸入剤・点眼剤など)でも臨床上問題となるDDIは起きますか?

    大谷 壽一

    薬局 (南山堂)  67 ( 8 ) 2457 - 2462 2016.07

    Introduction and explanation (commerce magazine), Single Work,  ISSN  0044-0035

  • Pharmacokinetic drug interactions of anti-invectives in the drug metabolism process

    OHTANI Hisakazu

    Antibiotics & Chemotherapy (医薬ジャーナル社)  31 ( 10 ) 1972 - 1979 2015.09

    Introduction and explanation (commerce magazine), Single Work,  ISSN  0913-2384

  • Structure of human placenta and drug permeation across the placenta

    OHTANI Hisakazu

    薬局 (南山堂)  66 ( 1 ) 54 - 59 2015.01

    Introduction and explanation (commerce magazine), Single Work,  ISSN  0044-0035

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Presentations 【 Display / hide

  • Pharmacy education in Japan - Clinical rotation and preceptorship -

    OHTANI Hisakazu

    Seminar National. Asosiasi Pendidikan Tinggi Farmasi Indonesia (APTFI) II (Banjarmasin, Indonesia) , 2017.11, Oral Presentation(guest/special), Association of Indonesian Pharmacy Higher Education (APTFI)

  • 医療連携で薬剤師に求められる臨床薬物動態学の基本

    OHTANI Hisakazu

    日本薬学会関東支部 薬剤師向け研修講演会 (前橋) , 2017.10, Public discourse, seminar, tutorial, course, lecture and others, 日本薬学会関東支部

    yakuzaishi2017.pdf

  • 受理される論文・されない論文

    OHTANI Hisakazu

    第1回 医療薬学教育セミナー (東京) , 2017.04, Public discourse, seminar, tutorial, course, lecture and others, 日本医療薬学会

  • イリノテカン誘発性消化管障害時におけるダビガトランの吸収動態変動とその要因

    HATTORI Tomoki, IMAOKA Ayuko, AKIYOSHI Takeshi, OHTANI Hisakazu

    日本薬学会第 137 年会 (仙台) , 2017.03, Oral Presentation(general)

  • グレープフルーツジュース成分および resveratrol の CYP2C9 阻害特性解析

    UCHIYAMA Marika, AKIYOSHI Takeshi, IMAOKA Ayuko, OHTANI Hisakazu

    日本薬学会第 137 年会 (仙台) , 2017.03, Poster (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • CYP2Cs及びOATPsを介した薬物ー飲食物間相互作用とその個人差の定量的解明

    2018.04
    -
    2021.03

    日本学術振興会, Grant-in-Aid for Scientific Research, 大谷壽一, Research grant, Principal Investigator

  • Analysis of the inter-individual variations of food-drug interactions via CYP2Cs and OATPs

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 大谷 壽一, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • 薬物−飲食物間相互作用の強度に個人差をもたらす遺伝的要因の解明

    2015.04
    -
    2018.03

    日本学術振興会, Grant-in-Aid for Scientific Research, 大谷壽一, Principal Investigator

  • Quantitative analysis of the factors that confer inter-individual variation of the extent of beverage-drug interactions

    2015.04
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 大谷 壽一, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • P450のMBIを介した薬物相互作用に個人差をもたらす遺伝的要因の定量的解明

    2012.04
    -
    2015.03

    Grant-in-Aid for Scientific Research, Hisakazu Ohtani, Research grant, Principal Investigator

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Awards 【 Display / hide

  • 年会優秀発表賞

    "丹羽しおり, 秋好健志, 今岡鮎子, 大谷壽一.", 2014.03, 日本薬学会第134年会, In vitro データをもとにした、CYP2D6 variants における paroxetine の非線型体内動態の予測.

  • 最優秀ポスター賞

    "三井梨恵子, 秋好健志, 今岡鮎子, 大谷壽一.", 2013.08, 医薬品情報学会 (第16回日本医薬品情報学会総会・学術大会), 免疫抑制剤、βblocker、ステロイドの低用量域における全身性副作用の用量依存性評価.

  • 優秀発表賞

    "○青野いづみ, 桑原亜記, 今井奈津美, 剱田侑希, 手塚淑人, 門田佳子, 小林典子, 鈴木小夜, 大谷壽一, 佐伯晴子, 木津純子.", 2013.03, 日本薬学会第133年会, 学生主体で構築した新たな服薬指導事前実習の評価.

  • 優秀ポスター賞

    "秋好健志, 齊藤隆志, 村瀬沙織, 宮崎光江, 中村克徳, 中村智徳, Guengerich F, Peter, 山本康次郎, 大谷壽一.", 2010.07, 医療薬学フォーラム2010/第18回クリニカルファーマシーシンポジウム, CYP3A4 変異型分子種の代謝活性に対する阻害剤の阻害強度の比較.

  • 日本医療薬学会奨励賞

    2007.09, 日本医療薬学会, 薬物動態・動力学の活用によるテーラーメイド処方設計支援システムの基盤技術の確立

    Country: 日本

 

Courses Taught 【 Display / hide

  • STUDY OF MAJOR FIELD: (CLINICAL PHARMACOKINETICS)

    2021

  • SEMINAR:(CLINICAL PHARMACOKINETICS)

    2021

  • RESEARCH FOR BACHELOR'S THESIS 1

    2021

  • PRIOR LEARNING FOR CLINICAL PRACTICE 2

    2021

  • PRE-CLINICAL TRAINING FOR HOSPITAL & COMMUNITY PHARMACY

    2021

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Courses Previously Taught 【 Display / hide

  • 薬学への招待

    Keio University, 2015, Spring Semester, Major subject, Lecture

  • C16(2)剤形をつくる

    Keio University, 2015, Autumn Semester, Major subject, Lecture

  • C15(3)テーラーメイド薬物治療を目指して

    Keio University, 2015, Spring Semester, Major subject, Lecture, Within own faculty

  • 臨床物理薬剤・製剤学

    Keio University, 2015, Spring Semester, Major subject, Lecture

  • 老年薬学と在宅医療

    Keio University, 2015, Autumn Semester, Lecture

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Educational Activities and Special Notes 【 Display / hide

  • 第3回アジア薬科大学連合 Deans Forum "Regional Harmonization of Pharmacy Education in Asia" (組織委員・座長・ポスター発表)

    2014.06

    , Lecture at Education Method and Practice

 

Social Activities 【 Display / hide

  • JGSDF (Japanese Army) Reserve

    2011.11
    -
    Present

     View Summary

    Reserve Major (Pharmacy Officer)

Memberships in Academic Societies 【 Display / hide

  • The Pharmaceutical Society of Japan, 

    1990
    -
    Present
  • 日本医療薬学会, 

    1997
    -
    Present
  • Japanese Society of Drug Informatics (JASDI)

     
  • 日本薬理学会

     

Committee Experiences 【 Display / hide

  • 2019.02
    -
    2021.01

    臨時委員, 薬事・食品衛生審議会

     View Remarks

    医薬品第一部会

  • 2011.04
    -
    2017.03

    Committee Member, Pharmacist License Examination Committee

  • 2009.05
    -
    2021.03

    Expert Committee Member, Pharmaceuticals and Medical Devices Agency

  • 2013.02
    -
    2015.01

    代議員, 日本薬学会

  • 2012.04
    -
    2015.03

    Editor, The Pharmaceutical Society of Japan

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