Gender differences in pharmacokinetics of alcohol.
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.
Baraona
E
E
Section of Liver Disease, Alcohol Research Center, Bronx Veterans Affairs and Mount Sinai Medical Centers, New York 10468, USA.
Abittan
C S
CS
Dohmen
K
K
Moretti
M
M
Pozzato
G
G
Chayes
Z W
ZW
Schaefer
C
C
Lieber
C S
CS
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D019540:Area Under Curve; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005746:Gastric Emptying / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008297:Male; D012737:Sex Factors; D018709:Statistics, Nonparametric
D002492:Central Nervous System Depressants; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent