Ethanol, acetaldehyde, acetate, and lactate levels after alcohol intake in white men and women: effect of 4-methylpyrazole

Alcohol Clin Exp Res. 2002 Feb;26(2):239-45.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaldehyde / analysis
  • Acetaldehyde / blood*
  • Acetates / blood
  • Adult
  • Alcohol Dehydrogenase / antagonists & inhibitors
  • Breath Tests
  • Enzyme Inhibitors / pharmacology
  • Ethanol / administration & dosage*
  • Ethanol / analysis
  • Ethanol / blood*
  • Female
  • Fomepizole
  • Humans
  • Lactic Acid / blood*
  • Male
  • Placebos
  • Premenopause
  • Pyrazoles / pharmacology*
  • Sex Characteristics


  • Acetates
  • Enzyme Inhibitors
  • Placebos
  • Pyrazoles
  • Lactic Acid
  • Ethanol
  • Fomepizole
  • Alcohol Dehydrogenase
  • Acetaldehyde