Jan 1, 1976

Anaerobic release of fluoride from halothane. Relationship to the binding of halothane metabolites to hepatic cellular constituents

Drug Metabolism and Disposition : the Biological Fate of Chemicals
R A Van Dyke, A J Gandolf

Abstract

Halothane has been found to undergo a reductive defluorination. This reaction requires an active cytochrome P-450 system and NADPH, and is inducible by phenobarbital and polychlorinated biphenyls but not by methylcholanthrene. The fluoride release occurs only under low O2 tension, while high O2 tension results in the oxidation of halothane to trifluoroacetic acid, inorganic bromide, and chloride. The release of the inorganic fluoride is linear up to 60 min. Because the conditions required for fluoride release and the binding of a halothane metabolite to microsomal phospholipids are similar, the defluorinated halothane molecule is assumed to be involved with this binding. However, based on the amount of fluoride released, the defluorinated halothane metabolite represents only approximately 60% of the total amount of halothane metabolite bound, which suggests that more than one metabolite may be involved in the binding.

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Mentioned in this Paper

20-Methylcholanthrene
Halothane
Fluoride Measurement
Aerobiosis
Cytochrome P450
Methylcholanthrene
Hepatic
Microsomes, Liver
Oxidation
Phenobarbital

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