Time-course of formation of volatile reductive metabolites of halothane in humans and an animal model.
The time-course of the formation of 2-chloro-1,1,1-trifluoroethane (CTF) and 2-chloro-1-1-difluoroethylene (CDF), two recently identified volatile reductive metabolites of halothane, has been studied in four patients receiving 1% halothane with 99% oxygen. The concentrations of CTF and CDF in end-expired breath increased with time and reached a plateau after approximately 60 min from commencing administration. A similar time-course and plateau was seen when Fischer 344 rats were anaesthetized with halothane 1% in oxygen. However, there was an eight-fold and 12-fold increase in CTF and CDF concentrations respectively when halothane 1% was administered under conditions of mild hypoxia (oxygen 14% inspired) to rats pretreated with phenobarbitone (this results in a marked increase in serum alanine aminotransferase (ALT) and necrotic damage in the vicinity of the central veins of the liver). It is suggested that breath concentrations of CDF and CTF provide a sensitive method of monitoring the reductive metabolism of halothane.
D000328:Adult; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000378:metabolism*; D017402:Chlorofluorocarbons; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D005030:Ethylenes / Q000378:metabolism*; D005260:Female; D006221:Halothane / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D017402:Chlorofluorocarbons; D005030:Ethylenes; D006846:Hydrocarbons, Halogenated; C016800:1,1,1-trifluoro-2-chloroethane; C018483:2-chloro-1,1-difluoroethylene; D006221:Halothane; D010634:Phenobarbital