Gastric origin of the first-pass metabolism of ethanol in humans: effect of gastrectomy

Abstract

The areas under the curve (AUCs) of blood ethanol concentrations are much smaller after oral than after intravenous administration of a small dose of ethanol. To study whether this difference is due to ethanol oxidation in the stomach, in the small intestine, or during first pass through the liver, we compared the AUCs after random administration of the same ethanol dose by the intravenous, oral, and intraduodenal routes to 5 abstaining alcoholics and via the two former routes to 10 subjects with Billroth II subtotal gastrectomy. In the nonoperated subjects, the AUCs after an ethanol dose (0.15 g/kg) given orally were 17% (p less than 0.01) of those achieved intravenously, in spite of the fact that greater than 99% of the dose had disappeared from the stomach at the completion of the AUC. By contrast, the AUCs after intraduodenal administration did not differ from those produced intravenously, indicating that neither the intestine nor the liver make a detectable contribution to this first-pass metabolism. Moreover, gastrectomy completely abolished the first-pass metabolism of ethanol. Gastric metabolism decreases the bioavailability of the ingested alcohol and thus attenuates its systemic toxicity. The abolition of this "protective barrier" in gastrectomized patients may increase their vulnerability to ethanol.