Abstract: AimTo study the drug metabolizing enzymes involved in the metabolism of bicyclol and identify the major metabolites of bicyclol in rat and human liver microsomes. MethodsBicyclol was incubated with rat and human liver microsomes. The metabolites of bicyclol were isolated by HPLC and identified by MS and ¹H NMR. ResultsThe metabolic rate of bicyclol in DEX-induced rat liver microsomes was obviously higher than that in untreated microsomes, while it was much lower in human liver microsomes. Ketoconazole was capable to exhibit strong inhibition (>90%) on bicyclol metabolism. Two metabolites of bicyclol were identified to be 4-hydroxy-4′-methoxy-6-hydroxy-methyl-6′-methoxycarbonyl-2,3,2′,3′-bis(methylene-dioxy) biphenyl and 4-methoxy-4′-hydroxy-6- hydroxymethyl-6′-methoxycarbonyl-2,3,2′,3′-bis(methylene-dioxy) biphenyl. ConclusionCYP3A was considered as the major catalyst involved in bicyclol metabolism in vitro and two metabolites of bicyclol in rats were identified as 4-hydroxy-4′-methoxy-6-hydroxy-methyl-6′-methoxycarbonyl-2,3,2′,3′-bis(methylene-dioxy) biphenyl and 4-methoxy-4′-hydroxy-6- hydroxymethyl-6′-methoxycarbonyl-2,3,2′,3′-bis(methylene-dioxy) biphenyl.