ABSTRACT
AIM: To study the drug metabolizing enzymes involved in the metabolism of bicyclol and identify the major metabolites of bicyclol in rat and human liver microsomes. METHODS: Bicyclol was incubated with rat and human liver microsomes. The metabolites of bicyclol were isolated by HPLC and identified by MS and 1H NMR. RESULTS: The 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. CONCLUSION: CYP3A 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 (methylenedioxy) biphenyl.
