Details of a Researcher - Ohtani, Hisakazu

Ohtani, Hisakazu

写真a

Affiliation: School of Medicine, Department of Clinical Pharmacy (Shinanomachi)

Position: Professor

Related Websites

https://www.keio-clin-pk.com

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

Other Affiliation 【 Display / hide 】

Keio University Hospital, Department of Pharmacy, Director
Faculty of Pharmacy, Department of Clinical Pharmacy, Concurrently appointed professor

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

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
JSCPT-Certified Pharmacist, 2021.12
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

Research Areas 【 Display / hide 】

Life Science / Clinical pharmacy (Clinical Pharmaceutical Science)
Life Science / 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
世界第一簡單藥物動力學 (「マンガでわかる薬物動態学」中国語(繁字)版)

大谷　壽一, 世茂出版有限公司, 2022.10, Page： 192
만화로 쉽게 배우는 약물동태학 (「マンガでわかる薬物動態学」韓国語版)

大谷　壽一, 성안당, 2022.08, Page： 192
スタンダード薬学シリーズII 6 医療薬学 V.薬物治療に役立つ情報 (補訂版)

日本薬学会 (編), 東京化学同人, 2021.05

Scope: SBO 55, 56, 章末問題 (10〜14章)
臨床検査データブック 2021-2022.

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, 2021.01

Papers 【 Display / hide 】

The Effects of N-Glycosylation on the Expression and Transport Activity of OATP1A2 and OATP2B1

Kataoka H., Akiyoshi T., Uchida Y., Imaoka A., Terasaki T., Ohtani H.

Journal of Pharmaceutical Sciences (Journal of Pharmaceutical Sciences) 113 ( 5 ) 1376 - 1384 2024.05

ISSN 00223549

　View Summary

Organic anion transporting polypeptide (OATP)1A2 and OATP2B1 have potential N-glycosylation sites, but their influence remains unclear. This study aimed to identify the N-glycosylation sites of OATP1A2/2B1 and investigate their impact on the expression and function of OATP1A2/2B1. Human embryonic kidney cells expressing OATP1A2 or OATP2B1 (HEK293-OATP1A2/2B1) were exposed to tunicamycin, an N-glycosylation inhibitor, and a plasma membrane fraction (PMF) Western blot assay and an estrone 3-sulfate (E3S) uptake study were conducted. HEK293-OATP1A2/OATP2B1 cell lines with mutation(s) at potential N-glycosylation sites were established, and the Western blotting and uptake study were repeated. Tunicamycin reduced the PMF levels and E3S uptake of OATP1A2/OATP2B1. The Asn124Gln, Asn135Gln, and Asn492Gln mutations in OATP1A2 and Asn176Gln and Asn538Gln mutations in OATP2B1 reduced the molecular weights of the OATP molecules and their PMF levels. The PMF levels of OATP1A2 Asn124/135Gln, OATP1A2 Asn124/135/492Gln, and OATP2B1 Asn176/538Gln were further reduced. The maximum transport velocities of OATP1A2 Asn124Gln, OATP1A2 Asn135Gln, and OATP2B1 Asn176/538Gln were markedly reduced to 10 %, 4 %, and 10 % of the wild-type level, respectively. In conclusion, the N-glycans at Asn124 and Asn135 of OATP1A2 and those at Asn176 and Asn538 of OATP2B1 are essential for the plasma membrane expression of these molecules and also affect their transport function.
- Access to Document (DOI)
Comprehensive analysis of responses from ChatGPT to consumer inquiries regarding over-the-counter medications.

Kiyomiya K, Aomori T, Ohtani H

Die Pharmazie 79 ( 1 ) 24 - 28 2024.02

ISSN 0031-7144
- Access to Document (DOI)
Determination of single-molecule transport activity of OATP2B1 by measuring the number of transporter molecules using electrophysiological approach

Yajima K., Akiyoshi T., Sakamoto K., Suzuki Y., Oka T., Imaoka A., Yamamura H., Kurokawa J., Ohtani H.

Journal of Pharmacological Sciences (Journal of Pharmacological Sciences) 153 ( 3 ) 153 - 160 2023.11

ISSN 13478613

　View Summary

Transporter-mediated clearance is determined by two factors, its single-molecule clearance, and expression level. However, no reliable method has been developed to evaluate them separately. This study aimed to develop a reliable method for evaluating the single-molecule activity of membrane transporters, such as organic anion transporting polypeptide (OATP) 2B1. HEK293 cells that co-expressed large conductance calcium-activated potassium (BK) channel and OATP2B1 were established and used for the following experiments. i) BK channel-mediated whole-cell conductance was measured using patch-clamp technique and divided by its unitary conductance to estimate the number of channels on plasma membrane (QI). ii) Using plasma membrane fraction, quantitative targeted absolute proteomics determined the stoichiometric ratio (ρ) of OATP2B1 to BK channel. iii) The uptake of estrone 3-sulfate was evaluated to calculate the Michaelis constant and uptake clearance (CL) per cell. Single-molecule clearance (CLint) was calculated by dividing CL by QI·ρ. QI and ρ values were estimated to be 916 and 2.16, respectively, yielding CLint of 5.23 fL/min/molecule. We successfully developed a novel method to reliably measure the single-molecule activity of a transporter, which could be used to evaluate the influences of factors such as genetic variations and post-translational modifications on the intrinsic activity of transporters.
- Access to Document (DOI)
Irinotecan-induced gastrointestinal damage alters the expression of peptide transporter 1 and absorption of cephalexin in rats

Imaoka A., Hattori T., Akiyoshi T., Ohtani H.

Biopharmaceutics and Drug Disposition (Biopharmaceutics and Drug Disposition) 44 ( 5 ) 372 - 379 2023.10

ISSN 01422782

　View Summary

Irinotecan causes severe gastrointestinal damage, which may affect the expression of intestinal transporters. However, neither the expression of peptide transporter 1 (Pept1) nor the pharmacokinetics of Pept1 substrate drugs has been investigated under irinotecan-induced gastrointestinal damage. Therefore, the present study quantitatively investigated the effects of irinotecan-induced gastrointestinal damage on the intestinal expression of Pept1 and absorption of cephalexin (CEX), a typical Pept1 substrate, in rats. Irinotecan was administered intravenously to rats for 4 days to induce gastrointestinal damage. The expression of Pept1 mRNA and the Pept1 protein in the upper, middle, and lower segments of the small intestine of irinotecan-treated rats was assessed by quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. The pharmacokinetic profile of CEX was examined after its oral or intravenous administration (10 mg/kg). In irinotecan-treated rats, ∼2-fold increases in Pept1 protein levels were observed in all three segments, whereas mRNA levels remained unchanged. The oral bioavailability of CEX significantly decreased to 76% of that in control rats. The decrease in passive diffusion caused by intestinal damage may have overcome the increase in Pept1-mediated uptake. In conclusion, irinotecan may decrease the intestinal absorption of Pept1 substrate drugs; however, it increased the expression of intestinal Pept1.
- Access to Document (DOI)
病棟薬剤業務による医師・看護師の業務負担軽減の定量的評価

佐々木駿一, 津田壮一郎, 清宮啓介, 中田英夫, 村松博, 青森達, 大谷壽一

医療薬学 ((一社)日本医療薬学会) 49 ( 10 ) 357 - 364 2023.10

ISSN 1346-342X

　View Summary

特定機能病院における病棟薬剤業務の他職種の業務負担への貢献度を定量的に評価する目的で、病棟勤務の医師・看護師に対しアンケート調査を行い240名中147名(医師40名、看護師107名)から回答を得た(有効回答率61.3%)。医師・看護師の業務削減時間は病棟薬剤業務項目の中で持参薬業務が最も多く、平均の業務削減時間は看護師より医師の方が有意に多かった。平均の業務削減時間は、医師は経験年数の短い者が長い者より多かったが、看護師は経験年数による影響は無かった。病棟薬剤業務の評価は医師・看護師ともに高かった。病棟薬剤業務による業務削減時間を定量的に明らかにした報告はこれが最初である。

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

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

Ohtani, Hisakazu

科学研究費補助金研究成果報告書 2020
Quantitative analysis of the factors that confer inter-individual variation of the extent of beverage-drug interactions

Otani, Hisakazu

科学研究費補助金研究成果報告書 2017
The effect of gastrointestinal damage on drug absorption

Otani, Hisakazu

科学研究費補助金研究成果報告書 2017
Quantitative analysis of genetic factors affecting the extent of drug interactions via mechanism based inhibition of cytochrome P450

Otani, Hisakazu

科学研究費補助金研究成果報告書 2014

Reviews, Commentaries, etc. 【 Display / hide 】

PBPMに基づく薬剤師面談は外来患者の薬物治療の適正化とアドヒアランス向上をもたらす

神成はるか, 西松直美, 小谷宙, 櫻井洋臣, 村松博, 青森達, 大谷壽一

日本エイズ学会誌 ((一社)日本エイズ学会) 25 ( 4 ) 431 - 431 2023.11

ISSN 1344-9478
骨髄腫の薬物治療の留意点　薬物動態と薬物相互作用の視点から(Pharmacokinetic aspects of drugs used for the treatment of myeloma)

大谷壽一

International Journal of Myeloma ((一社)日本骨髄腫学会) 13 ( 3 ) 95 - 95 2023.05
薬物相互作用の科学的評価とpersonalized medicationへの応用

大谷壽一

TDM研究 ((一社)日本TDM学会) 39 ( 2 ) 38 - 38 2022.05

ISSN 0911-1026
MeDaCaアプリを活用した妊娠・授乳と薬相談　オンライン相談の取り組み

櫻井しおり, 三浦あす美, 鈴木靖奈, 小谷宙, 清宮啓介, 村松博, 青森達, 大谷壽一

日本薬学会年会要旨集 ((公社)日本薬学会) 142年会 27PO1 - pm2 2022.03

ISSN 0918-9823
OATP1A2 variantsの輸送活性に対する温度の影響

片岡寛樹, 冬木陽大, 秋好健志, 森田時生, 矢島広大, 今岡鮎子, 片山和浩, 大谷壽一

日本薬学会年会要旨集 ((公社)日本薬学会) 142年会 27PO6 - am1 2022.03

ISSN 0918-9823

Presentations 【 Display / hide 】

Drug-beverage interaction

Hisakazu Ohtani

29th Dubai International Pharmaceutical & Technologies Conference & Exhibition - DUPHAT (Dubai) ,

2023.01
,
Oral presentation (invited, special)
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)

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.

Awards 【 Display / hide 】

日本医療薬学会賞

2023.11, 日本医療薬学会, 薬物相互作用の個人差に関する医療薬学的研究

Type of Award： Award from Japanese society, conference, symposium, etc.
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.

Courses Taught 【 Display / hide 】

ADVANCED BODY SYSTEMS AND REGULATION

2024
ADVANCED PHARMACOKINETICS

2024
STUDY OF MAJOR FIELD: (CLINICAL PHARMACY)

2024
SEMINAR:(CLINICAL PHARMACY)

2024
RESEARCH FOR BACHELOR'S THESIS 1

2024

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

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 Lieutenant Colonel (Pharmacy Officer)

Media Coverage 【 Display / hide 】

スポットライト

株式会社ファーマシィ, TURNUP (第59号 P4〜P10) , 2022.10
薬機法違反、出品者は認識を　ネットオークションで健康食品に効能効果表示

産経新聞 (朝刊) , 2017.07
「がんが防げる」「アトピーが緩和される」　ヤフオクで薬機法違反の表示が溢れていた

J-Cast ニュース > ヘルス&ビューティー, 2017.04
ヤフオクに多数効能効果標ぼう食品　慶大薬学部・大谷教授らが調査

健康産業流通新聞, 2017.04
ヤフオクで違法出品‐健康食品に効能・効果表示

薬事日報社, Yakuji Nippo, Limited, 2017.03

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 】

2023.10

-

2029.09

Associate Member, Science Council of Japan
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