Gender Differences in Pharmacokinetics of Alcohol

Alcohol Clin Exp Res. 2001 Apr;25(4):502-7.

Abstract

Background: The enhanced vulnerability of women to develop alcohol-related diseases may be due to their higher blood alcohol levels after drinking, but the mechanism for this effect is debated.

Methods: Sixty-five healthy volunteers of both genders drank 0.3 g of ethanol/kg of body weight (as 5%, 10%, or 40% solutions) postprandially. Blood alcohol concentrations were monitored by breath analysis and compared with those after intravenous infusion of the same dose. First-pass metabolism was quantified (using Michaelis-Menten kinetics) as the route-dependent difference in the amount of ethanol reaching the systemic blood. Gastric emptying was assessed by nuclear scanning after intake of 300 microCurie of technetium-labeled diethylene triamine pentacetic acid in 10% ethanol. The activities of alcohol dehydrogenase isozymes were assessed in 58 gastric biopsies, using preferred substrates for gamma-ADH (acetaldehyde) and for final sigma-ADH (m-nitrobenzaldehyde) and a specific reaction of chi-ADH (glutathione-dependent formaldehyde dehydrogenase).

Results: Women had less first-pass metabolism than men when given 10% or 40%, but not 5%, alcohol. This was associated with lower gastric chi-ADH activity; its low affinity for ethanol could explain the greater gender difference in first-pass metabolism with high rather than with low concentrations of imbibed alcohol. Alcohol gastric emptying was 42% slower and hepatic oxidation was 10% higher in women. A 7.3% smaller volume of alcohol distribution contributed to the higher ethanol levels in women, but it did not account for the route-dependent effects.

Conclusions: The gender difference in alcohol levels is due mainly to a smaller gastric metabolism in females (because of a significantly lesser activity of chi-ADH), rather than to differences in gastric emptying or in hepatic oxidation of ethanol. The concentration-dependency of these effects may explain earlier discrepancies. The combined pharmacokinetic differences may increase the vulnerability of women to the effects of ethanol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alcohol Dehydrogenase / metabolism
  • Aldehyde Oxidoreductases / metabolism
  • Area Under Curve
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / blood
  • Central Nervous System Depressants / pharmacokinetics*
  • Ethanol / administration & dosage
  • Ethanol / blood
  • Ethanol / pharmacokinetics*
  • Female
  • Gastric Emptying / physiology
  • Gastric Mucosa / metabolism
  • Humans
  • Male
  • Sex Factors
  • Statistics, Nonparametric

Substances

  • Central Nervous System Depressants
  • Ethanol
  • Alcohol Dehydrogenase
  • Aldehyde Oxidoreductases
  • formaldehyde dehydrogenase, glutathione-independent