Gender Differences in Pharmacokinetics of Alcohol

Authors

  • Enrique Baraona,

    1. Sections of Liver Disease and Nutrition, Alcohol Research Center (EB, CSA, KD, CSL), and of Nuclear Medicine (ZWC, CS), Bronx Veterans Affairs and Mount Sinai Medical Centers, New York, New York, and University of Trieste, Italy (MM, GP).
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  • Chaim S. Abittan,

    1. Sections of Liver Disease and Nutrition, Alcohol Research Center (EB, CSA, KD, CSL), and of Nuclear Medicine (ZWC, CS), Bronx Veterans Affairs and Mount Sinai Medical Centers, New York, New York, and University of Trieste, Italy (MM, GP).
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  • Kazufumi Dohmen,

    1. Sections of Liver Disease and Nutrition, Alcohol Research Center (EB, CSA, KD, CSL), and of Nuclear Medicine (ZWC, CS), Bronx Veterans Affairs and Mount Sinai Medical Centers, New York, New York, and University of Trieste, Italy (MM, GP).
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  • Michelle Moretti,

    1. Sections of Liver Disease and Nutrition, Alcohol Research Center (EB, CSA, KD, CSL), and of Nuclear Medicine (ZWC, CS), Bronx Veterans Affairs and Mount Sinai Medical Centers, New York, New York, and University of Trieste, Italy (MM, GP).
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  • Gabriele Pozzato,

    1. Sections of Liver Disease and Nutrition, Alcohol Research Center (EB, CSA, KD, CSL), and of Nuclear Medicine (ZWC, CS), Bronx Veterans Affairs and Mount Sinai Medical Centers, New York, New York, and University of Trieste, Italy (MM, GP).
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  • Zev W. Chayes,

    1. Sections of Liver Disease and Nutrition, Alcohol Research Center (EB, CSA, KD, CSL), and of Nuclear Medicine (ZWC, CS), Bronx Veterans Affairs and Mount Sinai Medical Centers, New York, New York, and University of Trieste, Italy (MM, GP).
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  • Clara Schaefer,

    1. Sections of Liver Disease and Nutrition, Alcohol Research Center (EB, CSA, KD, CSL), and of Nuclear Medicine (ZWC, CS), Bronx Veterans Affairs and Mount Sinai Medical Centers, New York, New York, and University of Trieste, Italy (MM, GP).
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  • Charles S. Lieber

    Corresponding author
    1. Sections of Liver Disease and Nutrition, Alcohol Research Center (EB, CSA, KD, CSL), and of Nuclear Medicine (ZWC, CS), Bronx Veterans Affairs and Mount Sinai Medical Centers, New York, New York, and University of Trieste, Italy (MM, GP).
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  • Supported by NIH Grants AA11115, AA05934, the Department of Veterans Affairs, and the Kingsbridge Research Foundation.

Reprint requests: Charles S. Lieber, MD, Alcohol Research Center, Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468; Fax: 718-733-6257; E-mail: liebercs@aol.com

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 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.

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