Читать книгу Transporters and Drug-Metabolizing Enzymes in Drug Toxicity - Albert P. Li - Страница 68

in vitro studies with human hepatocytes suggest that inhibition of the transporter ABCB11 (bile salt export pump [BSEP]), leading to intracellular accumulation of the cytotoxic bile salts, may be a mechanism of nefazodone hepatotoxicity [122, 123]. Nefazodone was reported to inhibit the efflux transporters MDR1 and MRP2, demonstrating that the drug and its metabolites may interact with efflux transporters in vivo [124]. While BSEP inhibition has been associated with DILI as a result of bile salt accumulation, the involvement of MDR1 and MRP2 in hepatotoxicity has not yet been clearly established. One possibility is the increased accumulation of the parent drug or its toxic metabolites which are efflux transporter substrates.