Drug uptake transporters: model systems, recent advances, and clinical relevance


Richard B. Kim MD, FRCPC

Professor of Medicine, Physiology & Pharmacology, and Oncology

Chair, Division of Clinical Pharmacology

Department of Medicine

University of Western Ontario


Abstract: Drug transporters are now widely appreciated as important determinants governing drug absorption, excretion, and in many cases, extent of drug entry into target organs. There is also a greater appreciation that altered drug transporter function, whether due to genetic polymorphisms, drug-drug interactions, or environmental factors such as dietary constituents, can in many cases result in unexpected drug-induced toxicity in vivo.  More recently, drug uptake transporters which can facilitate the cellular accumulation of substrate drugs have been noted to be key determinants of drug disposition, response, and in some cases, unexpected toxicity.


In this presentation, a number of drug uptake transporters of interest to potential drug response and toxicity will be outlined. These include members of the Organic Anion Transporting Polypeptide (OATP) family of drug uptake transporters, bile acid transporters such as Bile Salt Export Pump (BSEP). Importantly, a number of in vitro cell-based systems used for assessing such transporters will be discussed as well as some of the issues relating to genetic polymorphisms in these transporters. In addition, key issues relating to non-human (eg rat or mouse) drug uptake transporters vs human transporters will also be discussed.