Can the liver account for first-pass metabolism of ethanol in the rat?

Although the liver has far more ethanol-metabolizing capacity than does the stomach, all first-pass metabolism of alcohol is said to occur in the gastric mucosa because hepatic alcohol dehydrogenase is saturated at low peripheral blood alcohol concentrations. We evaluated the ability of the liver to carry out first-pass metabolism in the rat by constructing a model of hepatic handling of ethanol based on the kinetics of ethanol clearance after intraperitoneal injection of alcohol. Because the efficiency of first-pass metabolism is influenced by the rate of delivery of ethanol, the absorption rate of oral alcohol (0.5 g/kg) was determined and applied to the model. The blood ethanol curves predicted by the model for ethanol delivered via the portal vein or via intravenous infusion were virtually identical to the ethanol curves observed in experimental animals with each of these routes of delivery. We conclude that the liver can account for all first-pass metabolism experimentally observed in the rat, and it is not necessary to postulate some extrahepatic site of first-pass metabolism, such as the stomach.