Читать книгу Transporters and Drug-Metabolizing Enzymes in Drug Toxicity - Albert P. Li - Страница 92

Troglitazone represents one of the first hepatotoxic drugs where the accumulation of intracellular bile salts to cytotoxic levels due to BSEP inhibition is a likely mechanism of its toxicity. The initial discovery of troglitazone‐mediated BSEP inhibition was observed in rats in vivo and in rat liver plasma membrane preparations. Troglitazone was found to induce cholestasis in male and female rats. Troglitazone was found to inhibit BSEP‐mediated taurocholate transport with an apparent K(i) value, 1.3 μM, while its conjugated metabolite, troglitazone sulfate, was a more potent inhibitor, with an apparent K(i) value of 0.23 μM [226, 227].