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; Micheline Piquette-Miller; Joseph W Polli; Frans G M Russel; Jason A Sprowl; Kimio Tohyama; Joseph A Ware; Saskia N de Wildt; Wen Xie; Kim L R Brouwer; International Transporter Consortium

doi:10.1002/cpt.1115

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

Clin Pharmacol Ther. 2018 Nov;104(5):900-915. doi: 10.1002/cpt.1115. Epub 2018 Jul 12.

Affiliations

¹ Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Kenilworth, New Jersey, USA.
² Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
³ Mechanistic Safety and Drug Disposition, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
⁴ Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
⁵ Department of Pharmaceutical, Social and Administrative Sciences, School of Pharmacy, D'Youville College School, Buffalo, New York, USA.
⁶ Drug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company, Fujisawa, Kanagawa, Japan.
⁷ Department of Small Molecule Pharmaceutical Sciences, Genentech, South San Francisco, California, USA.
⁸ 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.
⁹ Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁰ Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acute Disease*
Animals
Chronic Disease / drug therapy*
Drug Interactions
Drug-Related Side Effects and Adverse Reactions / etiology
Drug-Related Side Effects and Adverse Reactions / metabolism
Humans
Membrane Transport Modulators / metabolism
Membrane Transport Modulators / pharmacology*
Membrane Transport Proteins / drug effects*
Membrane Transport Proteins / genetics
Membrane Transport Proteins / metabolism*
Models, Biological
Pharmaceutical Preparations / metabolism*
Pharmacokinetics*
Risk Assessment

Substances

Membrane Transport Modulators
Membrane Transport Proteins
Pharmaceutical Preparations

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding