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Effect of ethanol on rates of elimination and metabolism of zoxazolamine, hexobarbital and warfarin sodium in the rat

Biochemical Pharmacology
Publication Date
DOI: 10.1016/0006-2952(72)90074-3
  • Biology
  • Medicine


Abstract Male rats were fed single doses of ethanol or isocaloric quantities of glucose, in solution, by stomach tube following a 6 hr fast and were injected with zoxazolamine, warfarin sodium or hexobarbital 2 or 17 hr later. Other rats were pair-fed a nutritionally adequate synthetic diet containing ethanol or isocaloric quantities of sucrose for 7–11 days, and were treated with drugs following a 17 hr fast. Plasma concentrations of each drug were determined at various intervals of time following the injections. Administration of one dose of ethanol significantly increased the rates of elimination of zoxazolamine and of hexobarbital from the circulation 17 hr later, but the rate of warfarin elimination was unchanged. Chronic ethanol feeding also increased the rate of zoxazolamine elimination; but this increase was not greater than that following acute ethanol feeding; warfarin elimination was again not altered. Rates of metabolism of the drugs by liver microsomes in vitro 17 hr after a single dose of ethanol or glucose mirrored the effects on elimination in vivo; they were significantly increased in the alcohol-treated rats in the case of zoxazolamine and hexobarbital, but not changed in the case of warfarin. The rates of elimination of zoxazolamine and warfarin from the circulation were significantly reduced in rats fed ethanol 2 hr before. It is concluded that acute ethanol intake may increase the rates of elimination of some drugs when the alcohol is no longer present, as a consequence of microsomal enzyme induction, and may decrease rates of drug elimination when alcohol is present in vivo, probably as a result of inhibition by ethanol of microsomal drug-metabolizing enzymes.

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