INVITRO METABOLISM OF HALOTHANE (2-BROMO-2-CHLORO-1,1,1-TRIFLUOROETHANE) BY HEPATIC MICROSOMAL CYTOCHROME-P-450

Abstract

Incubation of halothane, a volatile anesthetic, with rabbit liver microsomes in the presence of NADPH and oxygen resulted in formation of trifluoroacetic acid (TFAA). No TFAA was detected in the absence of NADPH or O2. TFAA was found when a 9000 .times. g supernatant fraction (with NADPH and O2) was used instead of the microsomal fraction. The 105,000 .times. g supernatant fraction (with NADPH and O2), however, did not produce detectable levels of TFAA. Phenobarbital pretreatment of the animals resulted in a significant increase in formation of TFAA and cytochrome P-450 content of microsomes. A good correlation was found between formation of TFAA and microsomal cytochrome P-450 levels. The amount of TFAA formed in hepatic microsomes was significantly inhibited by CO, SKF 525-A (2-diethylaminoethyl-2,2,-diphenylvalerate hydrochloride and p-chloromercuribenzoic acid. TFAA was formed when NADH was used as an electron donor instead of NADPH. The metabolism of halothane by the hepatic microsomal mixed-function oxidase system may be related to its hepatotoxicity.