Enflurane, Isoflurane, and Methoxyflurane Metabolism in Rat Hepatic Microsomes from Ethanol-treated Animals

Abstract

The effects of ethanol on the metabolism of enflurane, isoflurane, and methoxyflurane were investigated to determine if alterations in biotransformation of these agents occur as a result of this treatment. In vitro incubations of hepatic microsomes from rats pretreated with 10 days' ethanol vapor inhalation revealed a fourfold increase in inorganic fluoride from enflurane when compared with incubations of microsomes from unpretreated rats and from phenobarbital-pretreated rats. Isoflurane, while metabolized to a lesser extent than enflurane, showed a similar stimulation of metabolism. Methoxyflurane, while metabolized to a greater extent than either enflurane or isoflurane, had lesser fluoride production by the microsomes from ethanol-pretreated rats than microsomes from phenobarbital-pretreated rats, but greater fluoride production than that found in microsomes from unpretreated rats. Ethanol pretreatment did not alter the levels of cytochrome P-450 which is the enzyme responsible for such metabolism. This suggests that the altered metabolism involves either a specific P-450 isozyme or an unidentified enzyme.