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Gender differences in pharmacokinetics of alcohol
E Baraona1, C S Abittan, K Dohmen
1Section of Liver Disease, Alcohol Research Center, Bronx Veterans Affairs and Mount Sinai Medical Centers, New York 10468, USA.
Alcoholism, Clinical and Experimental Research
|May 1, 2001
Summary
Women experience higher blood alcohol levels due to significantly reduced gastric metabolism, primarily from lower chi-ADH enzyme activity. This pharmacokinetic difference, especially at higher alcohol concentrations, contributes to their increased vulnerability to alcohol-related diseases.
Area of Science:
- Pharmacology
- Gastroenterology
- Toxicology
Background:
- Women exhibit heightened susceptibility to alcohol-related diseases, often linked to elevated blood alcohol concentrations (BAC).
- The precise physiological mechanisms underlying this gender-based difference in BAC remain a subject of scientific investigation.
Purpose of the Study:
- To investigate the pharmacokinetic factors contributing to higher BAC in women after oral ethanol consumption.
- To elucidate the roles of first-pass metabolism, gastric emptying, and hepatic oxidation in gender-specific alcohol responses.
Main Methods:
- Sixty-five healthy volunteers consumed controlled doses of ethanol (0.3 g/kg) in varying concentrations (5%, 10%, 40%).
- Blood alcohol concentrations (BAC) were measured via breath analysis and compared to intravenous administration.
- First-pass metabolism was quantified, gastric emptying assessed using nuclear scanning, and alcohol dehydrogenase (ADH) isozyme activities analyzed in gastric biopsies.
Main Results:
- Women demonstrated reduced first-pass metabolism, particularly with 10% and 40% ethanol solutions, linked to lower gastric chi-ADH activity.
- Gastric emptying was slower in women, while hepatic oxidation was slightly higher.
- A smaller volume of distribution in women contributed to higher BAC, but did not fully explain route-dependent effects.
Conclusions:
- Reduced gastric metabolism, primarily due to lower chi-ADH activity in females, is the main driver of higher BAC, not gastric emptying or hepatic oxidation differences.
- The concentration-dependent nature of these metabolic differences may resolve prior conflicting findings.
- These combined pharmacokinetic variations likely enhance women's vulnerability to ethanol's adverse effects.
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