Supported by NIH Grants AA11115, AA05934, the Department of Veterans Affairs, and the Kingsbridge Research Foundation.
Gender Differences in Pharmacokinetics of Alcohol
Article first published online: 11 APR 2006
Alcoholism: Clinical and Experimental Research
Volume 25, Issue 4, pages 502–507, April 2001
How to Cite
Baraona, E., Abittan, C. S., Dohmen, K., Moretti, M., Pozzato, G., Chayes, Z. W., Schaefer, C. and Lieber, C. S. (2001), Gender Differences in Pharmacokinetics of Alcohol. Alcoholism: Clinical and Experimental Research, 25: 502–507. doi: 10.1111/j.1530-0277.2001.tb02242.x
- Issue published online: 11 APR 2006
- Article first published online: 11 APR 2006
- Received for publication August 31, 2000; accepted January 16, 2001.
- Gastric Emptying;
- Gastric Alcohol Dehydrogenase
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 μCurie 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 γ-ADH (acetaldehyde) and for ς-ADH (m-nitrobenzaldehyde) and a specific reaction of χ-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 χ-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 χ-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.