Volume 104, Issue 5 p. 900-915
Reviews

Disease-Associated Changes in Drug Transporters May Impact the Pharmacokinetics and/or Toxicity of Drugs: A White Paper From the International Transporter Consortium

Raymond Evers

Corresponding Author

Raymond Evers

Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Kenilworth, New Jersey, USA

Correspondence: Raymond Evers ([email protected]) or Kim L.R. Brouwer ([email protected])Search for more papers by this author
Micheline Piquette-Miller

Micheline Piquette-Miller

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

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Joseph W. Polli

Joseph W. Polli

Mechanistic Safety and Drug Disposition, GlaxoSmithKline, King of Prussia, Pennsylvania, USA

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Frans G.M. Russel

Frans G.M. Russel

Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands

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Jason A. Sprowl

Jason A. Sprowl

Department of Pharmaceutical, Social and Administrative Sciences, School of Pharmacy, D'Youville College School, Buffalo, New York, USA

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Kimio Tohyama

Kimio Tohyama

Drug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company, Fujisawa, Kanagawa, Japan

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Joseph A. Ware

Joseph A. Ware

Department of Small Molecule Pharmaceutical Sciences, Genentech, South San Francisco, California, USA

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Saskia N. de Wildt

Saskia N. de Wildt

Department of Pharmacology and Toxicology and Department of Intensive Care, Radboud University Medical Center, Nijmegen, The Netherlands, and Intensive Care and Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands

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Wen Xie

Wen Xie

Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Kim L.R. Brouwer

Kim L.R. Brouwer

Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA

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on behalf of the International Transporter Consortium

on behalf of the International Transporter Consortium

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First published: 14 May 2018
Citations: 84

Abstract

Drug transporters are critically important for the absorption, distribution, metabolism, and excretion (ADME) of many drugs and endogenous compounds. Therefore, disruption of these pathways by inhibition, induction, genetic polymorphisms, or disease can have profound effects on overall physiology, drug pharmacokinetics, drug efficacy, and toxicity. This white paper provides a review of changes in transporter function associated with acute and chronic disease states, describes regulatory pathways affecting transporter expression, and identifies opportunities to advance the field.

CONFLICT OF INTEREST

As an Associate Editor for Clinical Pharmacology & Therapeutics, Micheline Piquette-Miller was not involved in the review or decision process for this article.