THE CRITICAL ROLE OF THE RATE OF ETHANOL ABSORPTION IN THE INTERPRETATION OF STUDIES PURPORTING TO DEMONSTRATE GASTRIC METABOLISM OF ETHANOL

The area under blood ethanol concentration-time curves may be lower af ter ingestion vs. intravenous infusion of similar ethanol doses, a dif ference that has been attributed to first-pass metabolism in the gastr ic mucosa. Using a model of human hepatic ethanol metabolism, we predi cted the area under blood ethanol concentration-time curves and first- pass metabolism that would result from oral vs. intravenous ethanol. T his model accurately predicted reported differences in AUC after oral vs. intravenous ethanol. First-pass metabolism has been shown to disap pear when the stomach is bypassed via intraduodenal or portal vein inf usion of ethanol. Our model predicts that the efficiency of first-pass metabolism is extremely sensitive to the hepatic delivery rate of eth anol and the rapid ethanol delivery rate in bypass studies would have eliminated hepatic first-pass metabolism. We conclude that hepatic eth anol metabolism could explain published observations concerning first- pass metabolism and it is not necessary to postulate a major role for gastric mucosal metabolism in this process. Inhibition of the liver's ability to oxidize ethanol is a necessary requirement of any theory pr oposing that the gastric mucosa is the primary site of first-pass etha nol metabolism.