Stimulatory effects of halothane and isoflurane on fluoride release and cytochrome P-450 loss caused by metabolism of 2-chloro-1,1-difluoroethene, a halothane metabolite.
The structural similarity of the halothane metabolite, 2-chloro-1,1-difluoroethene (CDE), to haloethenes that are metabolized by and inactivate cytochrome P-450, suggests that CDE may undergo secondary metabolism and degrade these isozymes. This possibility was examined in hepatic microsomes by determining fluoride release and cytochrome P-450 loss due to CDE metabolism in the presence of several anesthetics. CDE alone decreased cytochrome P-450 from phenobarbital-treated rats by as much as 37%, but the addition of isoflurane or halothane to incubations containing CDE increased the loss of cytochrome P-450 nearly twofold. Fluoride release was enhanced approximately 2.5 to 3 times by halothane or isoflurane; however, fluroxene inhibited fluoride release and did not enhance the loss of cytochrome P-450. Extrapolation of these results to the clinical situation suggests that the metabolism of CDE produced during halothane anesthesia and the accompanying cytochrome P-450 loss may contribute to the inhibition of drug metabolism produced by halothane.
D000818:Animals; D017402:Chlorofluorocarbons; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004987:Ethers / Q000378:metabolism; D005459:Fluorides / Q000378:metabolism*; D006221:Halothane / Q000378:metabolism / Q000494:pharmacology; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*; D007530:Isoflurane / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D017402:Chlorofluorocarbons; D065607:Cytochrome P-450 Enzyme Inhibitors; D004987:Ethers; D006846:Hydrocarbons, Halogenated; D003577:Cytochrome P-450 Enzyme System; D007530:Isoflurane; D005459:Fluorides; C018483:2-chloro-1,1-difluoroethylene; D010100:Oxygen; D006221:Halothane