REDUCTIVE METABOLISM OF HALOTHANE BY CYTOCHROME-P450 ISOFORMS IN RATSAND HUMANS

Cytochrome P450 (P450)-halothane complex formation, an index of reduct ive metabolism of halothane, was investigated by using rat hepatic mic rosomes and purified rat P450s under anaerobic conditions. P450-haloth ane complex formation was produced by the hepatic microsomes from phen obarbital and dexamethasone treated rats. Anti-P450 3A2 and 2B1/2 anti bodies extensively inhibited complex formation in hepatic microsomes f rom dexamethasone and phenobarbital treated rats, respectively. In rec onstituted systems using purified rat P450s, P450 3A2 and 2B1 complexe d halothane efficiently. Complex formation was also recognized in huma n hepatic microsomes under anaerobic conditions.