FIRST-PASS METABOLISM OF ALCOHOL - ABSENCE OF DIURNAL-VARIATION AND ITS INHIBITION BY CIMETIDINE AFTER EVENING MEAL

To determine whether the first-pass metabolism (FPM) of orally consume d alcohol varies with the time of day, 12 healthy male subjects were t ested with both oral and intravenous alcohol (0.3 g/kg), in the mornin g and evening, always 1 hr after the same standard meal. The results r evealed no significant differences in FPM (81.6 +/- 11.6 vs 99.8 +/- 1 0.6 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 H-2-antagonist that inhibits gastric alcohol dehydrogen ase activity in vitro. Compared to baseline, cimetidine (1 g/day for e ight 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 a lcohol (from 66 +/- 3 to 82 +/- 4%, P < 0.01), as well as peak blood a lcohol concentrations (from 4.3 +/- 0.4 to 5.9 +/- 0.5 mM, P < 0.05) a nd 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 possib le interaction with alcohol regardless of the time of day.