In Vitro Characterization of Hepatic Transporters OATP1B1 and OATP1B3

The hepatic transporters OATP1B1 and OATP1B3 contribute (to varying degrees, depending on the drug) to the uptake of many anionic drugs, including several of the widely used statins. Because statins are prescribed for many patients and the consequences of pharmacokinetic interactions with uptake inhibitors can be severe (even fatal), the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require that all NCEs be evaluated as inhibitors of OATP1B1 and OATP1B3. In addition, if hepatic clearance is expected to be a major pathway of elimination of an NCE, it must also be evaluated as a substrate of both transporters. Cell-based assays with over-expressing cell lines are useful for screening both substrates (based on uptake of the test compound) and inhibitors (based on interference with the uptake of a probe substrate by the test compound). The approach will be illustrated with real data, and subtle but important technical details will be discussed.