The role of CYP 3A4 and 1A1 in amiodarone-induced hepatocellular toxicity.

摘要: Amiodarone is a widely used potent antiarrhythmic for the treatment of cardiac disease; however, its use often discontinued due to numerous adverse effects, including hepatotoxicity. To investigate role drug metabolism in this liver toxicity, amiodarone and major metabolite desethylamiodarone were incubated with HepG2 cells overexpressing series cytochrome P450 (CYP) isoforms. Significantly higher cytotoxicity was observed CYP3A4 or CYP1A1, compared that empty vector transduced control cells. Further, levels more hepatotoxic detected CYP1A1 expressed The inhibitor ketoconazole α-naphthoflavone drastically inhibited desethylamiodarone. Along inhibition CYP3A4, significantly reduced. These data indicate by plays an important hepatocellular toxicity amiodarone.