Influence of Transporter Polymorphisms on Drug Disposition and Response: A Perspective From the International Transporter Consortium

Sook Wah Yee; Deanna J Brackman; Elizabeth A Ennis; Yuichi Sugiyama; Landry K Kamdem; Rebecca Blanchard; Aleksandra Galetin; Lei Zhang; Kathleen M Giacomini

doi:10.1002/cpt.1098

Influence of Transporter Polymorphisms on Drug Disposition and Response: A Perspective From the International Transporter Consortium

Clin Pharmacol Ther. 2018 Nov;104(5):803-817. doi: 10.1002/cpt.1098. Epub 2018 May 31.

Authors

Sook Wah Yee¹, Deanna J Brackman¹, Elizabeth A Ennis¹, Yuichi Sugiyama², Landry K Kamdem³, Rebecca Blanchard⁴, Aleksandra Galetin⁵, Lei Zhang⁶, Kathleen M Giacomini^{1

7}

Affiliations

¹ Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California, San Francisco, San Francisco, California, USA.
² Sugiyama Laboratory, RIKEN Innovation Center, Research Cluster for Innovation, RIKEN, Yokohama, Japan.
³ Department of Pharmaceutical Sciences, Harding University College of Pharmacy, Searcy, Arkansas, USA.
⁴ CRISPR Therapeutics, Cambridge, Massachusetts, USA.
⁵ Centre for Applied Pharmacokinetic Research, School of Health Sciences, University of Manchester, UK.
⁶ Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
⁷ Institute of Human Genetics, University of California, San Francisco, San Francisco, California, USA.

Abstract

Advances in genomic technologies have led to a wealth of information identifying genetic polymorphisms in membrane transporters, specifically how these polymorphisms affect drug disposition and response. This review describes the current perspective of the International Transporter Consortium (ITC) on clinically important polymorphisms in membrane transporters. ITC suggests that, in addition to previously recommended polymorphisms in ABCG2 (BCRP) and SLCO1B1 (OATP1B1), polymorphisms in the emerging transporter, SLC22A1 (OCT1), be considered during drug development. Collectively, polymorphisms in these transporters are important determinants of interindividual differences in the levels, toxicities, and response to many drugs.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Animals
Drug Interactions
Drug-Related Side Effects and Adverse Reactions / genetics
Drug-Related Side Effects and Adverse Reactions / metabolism
Genotype
Humans
Membrane Transport Proteins / genetics*
Membrane Transport Proteins / metabolism*
Pharmaceutical Preparations / metabolism*
Pharmacogenomic Variants*
Pharmacokinetics*
Phenotype
Polymorphism, Genetic*
Risk Assessment

Substances

Membrane Transport Proteins
Pharmaceutical Preparations

Abstract

Publication types

MeSH terms

Substances

Grants and funding