In vitro evidence for the role of OATP and OCT uptake transporters in drug-drug interactions

Background: Transport proteins, for example the drug export pump P-glycoprotein, are important for the absorption, distribution and excretion of drugs. Inhibition and induction of P-glycoprotein efflux function is a well-established mechanism of drug-drug interactions. Alteration of transporter-mediated drug uptake by concomitantly administered drugs may also result in a change in drug pharmacokinetics. These uptake transporter-mediated drug-drug interactions are the focus of this review. Objective: To examine the current in vitro evidence on interactions mediated by OATPs (organic anion transporting polypepticles) and OCTs (organic cation transporters). Methods: Comparing data of in vivo observed drug-drug interactions with in vitro analysed alterations in drug transport mediated by the hepatic expressed uptake transporters OATP1B1, OATP1B3 and OCT1 and by the renal expressed OCT2 protein. Results/conclusions: Some of the previously in vivo described drug-drug interactions could be explained by alteration in uptake transporter function demonstrating that inhibition or induction of uptake transporters is a newly recognised mechanism of potential drug-drug interactions.