title: First-pass metabolism of alcohol. Absence of diurnal variation and its inhibition by cimetidine after evening meal.
abstract: To determine whether the first-pass metabolism (FPM) of orally consumed alcohol varies with the time of day, 12 healthy male subjects were tested with both oral and intravenous alcohol (0.3 g/kg), in the morning and evening, always 1 hr after the same standard meal. The results revealed no significant differences in FPM (81.6 +/- 11.6 vs 92.8 +/- 10.6 mg/kg) or in any other index of alcohol absorption and metabolism. Eleven subjects were also tested in the evening after treatment with cimetidine, an H2-antagonist that inhibits gastric alcohol dehydrogenase activity in vitro. Compared to baseline, cimetidine (1 g/day for eight days) significantly decreased FPM (from 100.1 +/- 8.0 to 52.6 +/- 11.4 mg/kg, P < 0.01) and increased the systemic bioavailability of alcohol (from 66 +/- 3 to 82 +/- 4%, P < 0.01), as well as peak blood alcohol concentrations (from 4.3 +/- 0.4 to 5.9 +/- 0.5 mM, P < 0.05) and areas under the curve (from 5.1 +/- 0.5 to 7.0 +/- 0.5 mM/hr, P < 0.01). The results indicate the absence of diurnal variation in FPM and suggest that patients given cimetidine should be warned of its possible interaction with alcohol regardless of the time of day.
authors.affiliation: GI/Liver Program, Bronx VAMC, New York 10468, USA.
authors.forename: R
authors.initials: R
authors.lastname: Sharma
authors.forename: R T
authors.initials: RT
authors.lastname: Gentry
authors.forename: R T
authors.initials: RT
authors.lastname: Lim
authors.forename: C S
authors.initials: CS
authors.lastname: Lieber
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002927:Cimetidine / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000502:physiology*; D004435:Eating / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D012016:Reference Values; D013997:Time Factors
chemical_list: D000431:Ethanol; D002927:Cimetidine