Metabolic activation of the halothane metabolite, [14C]2-chloro-1,1-difluoroethene, in hepatic microsomes.
Halothane is reduced to 2-chloro-1,1,1-trifluoroethane (CTE) and 2-chloro-1,1-difluoroethene (CDE) by cytochrome P-450. These compounds may potentially undergo secondary metabolism in vivo, but their capacity to undergo metabolic activation and bind to macromolecules is unknown. This study, therefore, compared the abilities of CDE and CTE to bind to microsomal components in relation to that of halothane in hepatic microsomes. The results show that CDE, in addition to halothane, binds to microsomes under conditions of cytochrome P-450 activity. While halothane bound predominantly to lipids under nitrogen, CDE bound mainly to protein under oxygen. No CTE binding under any conditions could be detected. On an equimolar basis, CDE binding to protein was approximately one-third of that of halothane under oxidative conditions, however, CDE binding was enhanced in the presence of halothane. The results support the hypothesis that CDE metabolism may contribute to the metabolic binding due to halothane exposures.
D000693:Anaerobiosis; D000818:Animals; D001711:Biotransformation; D017402:Chlorofluorocarbons; D006221:Halothane / Q000031:analogs & derivatives / Q000378:metabolism*; D006846:Hydrocarbons, Halogenated / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D017402:Chlorofluorocarbons; D006846:Hydrocarbons, Halogenated; C016800:1,1,1-trifluoro-2-chloroethane; C018483:2-chloro-1,1-difluoroethylene; D006221:Halothane