Excretion organic anion transporting polypeptide

Troglitazone sulfate (Ml, the main metabolite) undergoes biliary excretion and accounts for up to 85% of the dose in humans (Loi et al. 1999). In patients with hepatic impairment, troglitazone sulfate was found to accumulate about fourfold in plasma with a threefold increased half-life (Ott et al. 1998 Loi et al. 1999). This metabolite also inhibited the canalicular bile salt export pump (Bsep), organic anion transporting polypeptide (OATP) transporters as well as drug transporters, suggesting it contributes to the hepatotoxicity. 

---