Membrane transporters in drug development and as determinants of precision medicine

被引：54

作者：

Galetin, Aleksandra ^{[1
]}

Brouwer, Kim L. R. ^{[2
]}

Tweedie, Donald ^{[3
]}

Yoshida, Kenta ^{[3
]}

Sjostedt, Noora ^{[4
]}

Aleksunes, Lauren ^{[5
]}

Chu, Xiaoyan ^{[6
]}

Evers, Raymond ^{[7
]}

Hafey, Michael J. ^{[6
]}

Lai, Yurong ^{[8
]}

Matsson, Par ^{[9
]}

Riselli, Andrew ^{[10
]}

Shen, Hong ^{[11
]}

Sparreboom, Alex ^{[12
]}

Varma, Manthena V. S. ^{[13
]}

Yang, Jia ^{[10
]}

Yang, Xinning ^{[14
]}

Yee, Sook Wah ^{[10
]}

Zamek-Gliszczynski, Maciej J. ^{[15
]}

Zhang, Lei ^{[16
]}

Giacomini, Kathleen M. ^{[10
]}

机构：

[1] Univ Manchester, Ctr Appl Pharmacokinet Res, Sch Hlth Sci, Manchester, England

[2] Univ North Carolina Chapel Hill, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA

[3] Clin Pharmacol, Genentech Res & Early Dev, South San Francisco, CA USA

[4] Univ Helsinki, Fac Pharm, Div Pharmaceut Biosci, Helsinki, Finland

[5] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmacol & Toxicol, Piscataway, NJ USA

[6] Merck & Co Inc, Dept Pharmacokinet Dynam Metab & Bioanalyt, Rahway, NJ USA

[7] Preclin Sci & Translat Safety, Johnson & Johnson, Janssen Pharmaceut, Spring House, PA USA

[8] Gilead Sci Inc, Drug Metab, Foster City, CA USA

[9] Univ Gothenburg, Sahlgrenska Acad, Dept Pharmacol, Gothenburg, Sweden

[10] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA

[11] Bristol Myers Squibb Res & Dev, Dept Drug Metab & Pharmacokinet, Princeton, NJ USA

[12] Ohio State Univ, Coll Pharm, Div Pharmaceut & Pharmacol, Columbus, OH USA

[13] Pfizer Inc, Pharmacokinet Dynam & Metab, Med Design, Worldwide R&D, Groton, CT USA

[14] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA

[15] Drug Metab & PK, GlaxoSmithKline, Collegeville, PA USA

[16] US FDA, Off Res & Stand, Off Gener Drugs, Ctr Drug Evaluat & Res CDER, Silver Spring, MD USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2024年 / 23卷 / 04期

基金：

美国国家卫生研究院;

关键词：

MDCK CELL-LINE; IN-VITRO; ENDOGENOUS BIOMARKERS; METABOLIZING-ENZYMES; EFFLUX TRANSPORTERS; P-GLYCOPROTEIN; HEPATIC-UPTAKE; QUANTITATIVE PROTEOMICS; SIMVASTATIN ACID; UPTAKE CLEARANCE;

D O I：

10.1038/s41573-023-00877-1

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The effect of membrane transporters on drug disposition, efficacy and safety is now well recognized. Since the initial publication from the International Transporter Consortium, significant progress has been made in understanding the roles and functions of transporters, as well as in the development of tools and models to assess and predict transporter-mediated activity, toxicity and drug-drug interactions (DDIs). Notable advances include an increased understanding of the effects of intrinsic and extrinsic factors on transporter activity, the application of physiologically based pharmacokinetic modelling in predicting transporter-mediated drug disposition, the identification of endogenous biomarkers to assess transporter-mediated DDIs and the determination of the cryogenic electron microscopy structures of SLC and ABC transporters. This article provides an overview of these key developments, highlighting unanswered questions, regulatory considerations and future directions. Significant progress has been made in understanding the influence of membrane transporters in drug disposition and response. Here, the International Transporter Consortium provides an update on the current status of membrane transporters in drug development and regulatory requirements, discusses recent scientific advances in the field and highlights future directions and unanswered questions.

引用

页码：255 / 280

页数：26

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