CAN THE LIVER ACCOUNT FOR FIRST-PASS METABOLISM OF ETHANOL IN THE RAT

Although the liver has far more ethanol-metabolizing capacity than doe s the stomach, all first-pass metabolism of alcohol is said to occur i n the gastric mucosa because hepatic alcohol dehydrogenase is saturate d at low peripheral blood alcohol concentrations. We evaluated the abi lity of the liver to carry out first-pass metabolism in the rat by con structing a model of the hepatic handling of ethanol based on the kine tics of ethanol clearance after intraperitoneal injection of alcohol. Because the efficiency of first-pass metabolism is influenced by the r ate 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 v ia intravenous infusion were virtually identical to the ethanol curves observed in experimental animals with each of these routes of deliver y. We conclude that the liver can account for all first-pass metabolis m experimentally observed in the rat, and it is not necessary to postu late some extrahepatic site of first-pass metabolism, such as the stom ach.