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First pass metabolism of ethanol

C S Lieber1, R T Gentry, E Baraona

  • 1Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, NY, USA.

Alcohol and Alcoholism (Oxford, Oxfordshire). Supplement
|January 1, 1994
PubMed
Summary

The human stomach metabolizes ethanol, reducing its systemic effects through first-pass metabolism (FPM). Factors like gastrectomy, alcohol consumption, fasting, and certain medications can impair this protective gastric metabolism, increasing blood alcohol levels.

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Gastroenterology

Background:

  • The human stomach possesses alcohol dehydrogenase (ADH) isozymes with varying affinities for ethanol.
  • Gastric ADH activity contributes to the first-pass metabolism (FPM) of ethanol, influencing its bioavailability.
  • This gastric metabolism acts as a protective barrier against systemic ethanol effects.

Purpose of the Study:

  • To document the role of gastric ethanol metabolism in vivo.
  • To investigate factors affecting gastric ethanol metabolism and FPM.
  • To understand the clinical relevance of gastric ADH activity and its modulation by drugs.

Main Methods:

  • In vitro studies of ADH isozymes and drug effects.
  • In vivo experiments involving intraduodenal, intraportal, and intragastric ethanol administration.

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  • Pylorus ligation and gastrectomy models to assess gastric contribution to ethanol metabolism.

    • Main Results:

    • Gastric administration resulted in lower blood alcohol levels compared to intestinal routes, confirming gastric metabolism's role.
    • Gastrectomy eliminated this protective effect, while conditions like fasting and certain medications reduced gastric ADH activity.
    • Drug interactions (aspirin, acetaminophen, H2-blockers) and physiological states (fasting, gender, alcohol consumption) significantly impact FPM.

    Conclusions:

    • The stomach plays a clinically relevant role in ethanol metabolism via FPM.
    • Factors such as surgery, physiological conditions, and common medications can significantly alter gastric ethanol metabolism.
    • Impaired gastric metabolism leads to increased systemic blood alcohol concentrations, particularly at lower doses.