Abstract
Halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) releases inorganic fluoride when incubated anaerobically with rat hepatic microsomes reduced with either NADPH or sodium dithionite. Boiled microsomes (cytochrome P-420), hemoglobin, and hemin, each reduced with sodium dithionite, also catalyze the release of inorganic fluoride from halothane, suggesting that the protein portion of cytochrome P-450 is not required for reductive halothane defluorination. 2-Chloro-1,1-difluoroethylene and its bromo analog 2-bromo-1,1-difluoroethylene undergo metabolism in NADPH-reduced microsomes with optimal release of fluoride occurring under air compared to an atmosphere of nitrogen. Neither 2-chloro-1,1,1-trifluoroethane nor 2-bromo-1,1,1-trifluoroethane liberate fluoride in microsomes under air or nitrogen. 2-Chloro-1,1-difluoroethylene and 2-bromo-1,1-difluoroethylene are metabolized predominantly by oxidative cytochrome P-450 metabolism, while reductive pathways utilizing reduced cytochrome P-450, hemoglobin, or hemin liberate fluoride from halothane.
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