Ohtani, Hisakazu

写真a

Affiliation

School of Medicine, Department of Clinical Pharmacy （Shinanomachi）

Position

Professor

External Links
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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。

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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

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Other Affiliation 【 Display / hide 】

  • Keio University Hospital, Department of Pharmacy, Director

  • Faculty of Pharmacy, Department of Clinical Pharmacokinetics, Concurrently appointed professor

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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

    Kyushu University, Graduate School of Pharmaceutical Sciences, Associate Professor

  • 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

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Academic Degrees 【 Display / hide 】

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

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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 】

  • Life Science / Clinical pharmacy (Clinical Pharmaceutical Science)

  • Life Science / Pharmacology (Applied Pharmacology)

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Research Keywords 【 Display / hide 】

  • pharmacometrics

  • personalized medication

  • interindividual variation of pharmacokinetics

  • drug interactions

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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 2019-2020.

    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, 2019.01

  • 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

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Papers 【 Display / hide 】

  • Analysis of inhibition kinetics of three beverage ingredients, bergamottin, dihydroxybergamottin and resveratrol, on CYP2C9 activity

    Akiyoshi T., Uchiyama M., Inada R., Imaoka A., Ohtani H.

    Drug Metabolism and Pharmacokinetics （Drug Metabolism and Pharmacokinetics)  42   100429 2022.02

    Research paper (scientific journal), Accepted,  ISSN  13474367

    　View Summary

    Some grapefruit juice (GFJ) ingredients and resveratrol, a fruit-derived phytoalexin, are known to inhibit cytochrome P450 (CYP) 2C9. However, their inhibition modes and detailed inhibition kinetics remain undetermined. This study aimed to investigate the inhibitory effects of two GFJ ingredients, bergamottin (BG) and dihydroxybergamottin (DHB), and resveratrol on CYP2C9 activity in vitro. DHB inhibited CYP2C9 activity, as assessed by warfarin 7-hydroxylation, in a preincubation time-dependent manner (i.e., mechanism-based inhibition; MBI), in the same manner as CYP2C19 and CYP3A4. The maximal inactivation rate (kinact,max) was 0.0638 min−1 and 0.12- and 0.26-fold of that for CYP2C19 and CYP3A4, respectively. BG showed both MBI and time-independent competitive inhibition. Resveratrol showed non-competitive inhibition with an inhibition constant (Ki) of 3.64 μM. Unlike the inhibition of CYP2C19 and CYP3A4, resveratrol did not induce MBI. These findings are important for estimating the risk of drug interactions between CYP2C9 substrates and some beverages. (146 words)

  • Mechanistic bottom-up estimation of passive drug absorption from the gastrointestinal tract– Comparison among primary cultured human intestinal cells, Caco-2 cells, artificial membranes, and animal scale-up

    Tsuchitani T, Akiyoshi T, Imaoka A, Ohtani H

    Int J Clin Pharmacol Ther  2022

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0946-1965

  • Evaluation of hepatic CYP3A enzyme activity using endogenous markers in lung cancer patients treated with cisplatin, dexamethasone, and aprepitant.

    Hibino H, Sakiyama N, Makino Y, Makihara-Ando R, Horinouchi H, Fujiwara Y, Kanda S, Goto Y, Yoshida T, Okuma Y, Shinno Y, Murakami S, Hashimoto H, Akiyoshi T, Imaoka A, Ohe Y, Yamaguchi M, Ohtani H

    （Eur J Clin Pharmacol)   2022

    Research paper (scientific journal), Joint Work, Accepted

  • Dual kinetics of OATP2B1: Inhibitory potency and pH-dependence of OATP2B1 inhibitors

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

    Drug Metabolism and Pharmacokinetics （Drug Metabolism and Pharmacokinetics)  41   100416 2021.12

    Research paper (scientific journal), Accepted,  ISSN  13474367

    　View Summary

    Organic anion transporting polypeptide (OATP) 2B1 is expressed in the intestine and liver, and OATP2B1-mediated transport of estrone 3-sulfate is pH-dependent and consists of: the high-affinity component (Hc) and low-affinity component (Lc). This study aimed to evaluate the influence of pH on the transport kinetics of each component, along with the inhibitory nature of ten OATP2B1 inhibitors. The Michaelis constants (Km) were 4-fold and 1.5-fold lower at pH 6.3 than at pH 7.4, for Hc and Lc respectively. The inhibitory potencies of diclofenac, indomethacin, and ibuprofen towards Hc were 1.5–4.3 fold lower at pH 6.3 than at pH 7.4. Contrastingly, inhibitory potencies towards Lc were 9.0–52 fold lower at pH 7.4. Similarly, the inhibitory effect of naproxen was stronger towards Hc at pH 6.3 and towards Lc at pH 7.4. On the other hand, celecoxib selectively inhibited Lc transport at pH 7.4. Rifampicin inhibited both components at pH 6.3 and 7.4 to a similar extent, while bromosulphophthalein, naringin, and gefitinib selectively inhibited Hc irrespective of pH. Fexofenadine inhibited neither component. In conclusion, the transport affinities of both Hc and Lc were enhanced under acidic conditions. The influence of pH on the inhibitory potency towards each component varied among the inhibitors.

  • Time-dependent inhibition of CYP3A4-mediated midazolam metabolism by macrolide antibiotics in CYP3A4 genetic variants: Comparison with testosterone metabolism

    Akiyoshi Takeshi, Naitou Rina, Imaoka Ayuko, Miyazaki Mitsue, Guengerich F. Peter, Nakamura Katsunori, Yamamoto Koujiro, Ohtani Hisakazu

    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 59 （ 12 ） 745 - 752 2021.12

    Research paper (scientific journal), Accepted,  ISSN  0946-1965

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

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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 ) 1537 - 1537 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.

  • CYP2C19変異型分子種の代謝活性に及ぼす温度の影響

    趙 澄絵, 秋好 健志, 渡辺 大智, 関 博行, 今岡 鮎子, 山崎 浩史, 下地 みゆき, 中村 克徳, 大谷 壽一

    日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   28P - pm026S 2020.03

    ISSN  0918-9823

  • CYP2C9遺伝的変異型におけるresveratrolおよびsesaminの阻害特性の比較

    稲田 理乃, 秋好 健志, 今岡 鮎子, 大谷 壽一

    日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   28P - pm046S 2020.03

    ISSN  0918-9823

  • 5-FU曝露による消化管の薬物トランスポーターの経時的発現変化

    安藤 花乃莉, 秋好 健志, 今岡 鮎子, 大谷 壽一

    日本薬学会年会要旨集 ((公社)日本薬学会)  139年会 ( 4 ) 105 - 105 2019.03

    ISSN  0918-9823

  • CYP2C9各種遺伝的バリアントにおける代謝活性の温度依存性

    小島 行景, 秋好 健志, 今岡 鮎子, 大谷 壽一

    日本薬学会年会要旨集 ((公社)日本薬学会)  139年会 ( 4 ) 143 - 143 2019.03

    ISSN  0918-9823

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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 (invited, 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 lecture, seminar, tutorial, course, or other speech, 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 lecture, seminar, tutorial, course, or other speech, 日本医療薬学会

  • フェノバルビタールと活性炭の相互作用は食事により減弱する

    IMAOKA Ayuko, OGATA Yuka, AKIYOSHI Takeshi, OHTANI Hisakazu

    日本薬学会第 137 年会 (仙台) , 

    2017.03
    , 

    Oral presentation (general)

  • 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)

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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, 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, Ohtani Hisakazu, Grant-in-Aid for Scientific Research (C), Principal investigator

    　View Summary

    The mechanism of food-drug interactions includes the inhibition of metabolic enzymes or drug transporters, which have genetic variations. The aim of this study is to clarify whether the genetic variations of metabolic enzymes and transporters lead to the altered inhibitory kinetics of respective inhibitors contained in a variety of fruit juices. We focused upon two metabolic enzymes (CYP2C9 and CYP2C19) and two transporters (OATP1A2 and OATP2B1). Detailed analysis revealed that the inhibitory kinetics of various inhibitors highly differ among genetic variants. Therefore, the genetic variants of metabolic enzymes and drug transporters are considered to be one of the important factors to confer inter-individual variation in the extent of food-drug interactions. We also succeeded in identifying a novel OATP inhibitor, narirutin, from grape fruit juice.

  • 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, 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, Hisakazu OHTANI, AKIYOSHI Takeshi, IMAOKA Ayuko, Grant-in-Aid for Scientific Research (C), Principal investigator

    　View Summary

    The influences of genetic variation of CYP3A4 on the inhibitory kinetics of its inhibitors varied among the inhibitors and affected by the probe substrate used. The inhibitor manners (patterns) of metabolic inhibitors contained in fruit juice are different among CYP isoforms, i.e. CYP3A4, 2C9 and 2C19. The research should be focused upon the mode of inhibition that is clinically most relevant.
    Using newly developed cell lines stably expressing a transporter OATP1A2 or OATP2B1, some unidentified inhibitory ingredient(s) for these transporters are considered to be contained in some fractions of grapefruit juice.

  • Quantitative analysis of genetic factors affecting the extent of drug interactions via mechanism based inhibition of cytochrome P450

    2012.04
    -
    2015.03

    Keio University, Grant-in-Aid for Scientific Research, Hisakazu Ohtani, YAMAMOTO Koujirou, AKIYOSHI Takeshi, YAMAZAKI Hiroshi, Grant-in-Aid for Scientific Research (C), Research grant, Principal investigator

    　View Summary

    There seems to be considerable inter-individual variations in the extent of drug interactions, especially via the inhibition of oxidative metabolic enzymes, P450s. This study aimed to investigate quantitatively the influence of genetic variation of P450s, such as CYP3A4 and CYP2D6, on the extent of drug interaction in the in vitro studies using genetic variants. As a result of enzymatic study with probe substrates and mechanism-based inhibitors (MBI), we concluded that the inhibitory potencies of MBI differ among genetic variants. These results suggest that the genetic variation of metabolic enzymes affect the extent of drug interactions caused by their inhibitors, as well as the pharmacokinetics of their substrate drugs.

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Awards 【 Display / hide 】

  • 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

  • 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.

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Courses Taught 【 Display / hide 】

  • BACHELOR'S THESIS

    2022

  • ADVANCED PRACTICAL TRAINING IN A HOSPITAL (ABROAD)

    2022

  • ADVANCED PHARMACOKINETICS

    2022

  • ADVANCED BODY SYSTEMS AND REGULATION

    2022

  • CLINICAL PHARMACOLOGY

    2022

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Courses Previously Taught 【 Display / hide 】

  • 薬学への招待

    Keio University

    2015.04
    -
    2016.03
    , 

    Spring Semester, Lecture

  • C16(2)剤形をつくる

    Keio University

    2015.04
    -
    2016.03
    , 

    Autumn Semester, Lecture

  • C15(3)テーラーメイド薬物治療を目指して

    Keio University

    2015.04
    -
    2016.03
    , 

    Spring Semester, Lecture, Within own ｆaculty

  • 臨床物理薬剤・製剤学

    Keio University

    2015.04
    -
    2016.03
    , 

    Spring Semester, Lecture

  • 老年薬学と在宅医療

    Keio University

    2015.04
    -
    2016.03
    , 

    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

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Social Activities 【 Display / hide 】

  • JGSDF (Japanese Army) Reserve

    2011.11
    -
    Present

    　View Summary

    Reserve Lieutenant Colonel (Pharmacy Officer)

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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

    　
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Committee Experiences 【 Display / hide 】

  • 2019.02
    -
    Present

    臨時委員, 薬事・食品衛生審議会

    　View Remarks

    医薬品第一部会

  • 2009.05
    -
    Present

    Expert Committee Member, Pharmaceuticals and Medical Devices Agency

  • 2010.04
    -
    Present

    学術評議員, 日本薬理学会

  • 2009.04
    -
    Present

    Examination Committee Member, MR Education & Accreditation Center of Japan

  • 2018.04
    -
    2019.03

    医療薬科学部会長, 日本薬学会

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