Hepatic solute carrier transporters and drug therapy: Regulation of expression and impact of genetic variation

Organic cation transporters (OCT), organic anion transporting polypeptides (OATP) and organic anion transporters (OAT) from the solute carrier (SLC) family play an essential role in the uptake of endogenous compounds and drugs into the hepatocytes and other cell types. The well-documented interindividual variability of expression and activity of these transporters translates into interindividual variability in drug pharmacokinetics and drug response. It is therefore important to elucidate mechanisms affecting membrane transporter expression and function. These mechanisms include transcriptional regulation, disease-dependent regulation and genetic variation. In this review, we will summarize the current knowledge of the molecular functions and substrate profiles of cloned hepatic OCTs, OATPs and OATs and discuss recent advances in understanding variable expression and function. Finally, the role of genetic variation in these transporters on drug exposure will be presented with implications for individual drug response.