BSEP and MRP2 Transport Vesicle Screening Assays for the Prediction of Potential Cholestatic and Drug-Induced Liver Injury

In this study, we examined 18 potential cholestatic drugs in human BSEP/MRP2 and rat Bsep/Mrp2 membrane vesicle assays. These drugs are known to be BSEP inhibitors, MRP2 inhibitors, dual BSEP and MRP2 inhibitors or glutathione depleters. The data suggest a relatively strong association between the interference with BSEP and/or MRP2 functions and drug-induced liver toxicity. These results demonstrate the applicability of in vitro, vesicle-based BSEP and MRP2 inhibition approaches to limit or avoid liver liabilities in humans that are not often detected by standard preclinical animal models.