Contribution of gastric oxidation to ethanol first-pass metabolism in baboons

Background: A portion of ingested alcohol does not reach the systemic blood, undergoing a first-pass metabolism (FPM) during gastric and hepatic circulation. Methods: To determine whether the stomach can metabolize sufficient ethanol to account for the FPM, and to what extent gastric alcohol dehydrogenase (ADH) activity is responsible, the hepatic vein, the portal vein. and the aorta were cannulated nonocclusively in baboons to measure the conversion of ethanol to acetate in vivo. C-14-ethanol (300 mg/kg as a 15% solution) was given intragastrically (IG) whereas H-3-acetate was continuously infused intravenously (IV).C-14-acetate was measured after exhaustive evaporation of ethanol. Simultaneous sampling of hepatic venous, portal and arterial blood was carried out for 3 hr, at the end of which the same alcohol dose was given IV to calculate the Michaelis-Menten parameters of elimination. Results: Analysis of the IV and IG ethanol curves revealed a FPM of 94 +/- 11 mg/kg (31% of dose). The portal-arterial differences were negative for H-3-acetate (indicating net extraction) and positive for C-14-ethanol and C-14-acetate (indicating net output). Portal acetate production (extraction plus net output multiplied by the portal plasma flow) increased with time and accounted, over the first 3 hr (82 +/- 13 mg/kg), for 87% of the FPM. Alcohol oxidation by gastric ADH activity (28.7 +/- 7.2 mg/kg) accounted for only 31% of the FPM. Conclusions: The in vivo oxidation of ethanol to acetate in the upper digestive tract accounts for the FPM of ethanol and is mediated, at least in part, by ADH activity.