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

R. A. Van Dyke, A Jay Gandolfi

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)40-44
Number of pages5
JournalDrug Metabolism and Disposition
Volume4
Issue number1
StatePublished - 1976
Externally publishedYes

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Halothane
Metabolites
Fluorides
Liver
Trifluoroacetic Acid
Methylcholanthrene
Polychlorinated Biphenyls
Phenobarbital
Bromides
NADP
Cytochrome P-450 Enzyme System
Chlorides
Phospholipids
Oxidation
Molecules

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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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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T1 - Anaerobic release of fluoride from halothane. Relationship to the binding of halothane metabolites to hepatic cellular constituents

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N2 - 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.

AB - 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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