[Metabolism of bicyclol in rat and human liver microsomes in vitro].
OBJECTIVE
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.


CONCLUSIONS
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.
Ju
Mei-hua
MH
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Li
Yan
Y
D000328:Adult; D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D001713:Biphenyl Compounds; D003577:Cytochrome P-450 Enzyme System; C477843:bicyclol; D007654:Ketoconazole