Background: 4-Methylpyrazole (4-MP), a selective inhibitor of alcohol dehydrogenase (ADH), recently has been approved for clinical use in humans. The objective was to evaluate the use of 4-MP in human alcohol research and to study the effect of 4-MP on various parameters of alcohol metabolism during alcohol intoxication.
Methods: 4-MP (10-15 mg/kg orally) or placebo was given in double-blind fashion to 22 premenopausal women, 12 of whom were using oral contraceptives, and 13 men followed by intake of alcohol (0.5 g/kg orally) or placebo.
Results: A 30% to 40% decrease in the ethanol elimination rate was observed in the different groups during pretreatment with 4-MP. The alcohol-induced increase in plasma acetate was partially inhibited by 4-MP. A significant positive correlation was observed between the effect of 4-MP on the alcohol-induced lactate and acetate elevations. The acetaldehyde was nondetectable (<1 micromol/liter) in the peripheral venous blood during alcohol intoxication in both women and men. During alcohol intoxication, a decrease in breath acetaldehyde was found with 4-MP pretreatment in women but not in men.
Conclusion: The alcohol-induced elevation in blood acetate level is caused, in part, by ADH-mediated ethanol oxidation. Although no evidence was found for measurable acetaldehyde levels in the peripheral venous blood during alcohol intoxication, the effect of 4-MP on breath acetaldehyde in women supports the view that ADH-mediated acetaldehyde elevations reflected in the airways, but too low to be detected in the peripheral venous blood, may occur in women during alcohol intoxication in the present experimental conditions.