Characterization of human cytochrome P450 mediated bioactivation of amodiaquine and its major metabolite N‐desethylamodiaquine

摘要

AimsOxidative bioactivation of amodiaquine (AQ) by cytochrome P450s to a reactive quinoneimine is considered as an important mechanism underlying its idiosyncratic hepatotoxicity. However, because internal exposure to its major metabolite N‐desethylamodiaquine (DEAQ) is up to 240‐fold higher than AQ, bioactivation of DEAQ might significantly contribute to covalent binding. The aim of the present study was to compare the kinetics of bioactivation of AQ and DEAQ by human liver microsomes (HLM) and to characterize the CYPs involved in bioactivation of AQ and DEAQ.