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 after ingestion vs. intravenous infusion of similar ethanol doses, a difference that has been attributed to first-pass metabolism in the gastric mucosa. Using a model of human hepatic ethanol metabolism, we predicted the area under blood ethanol concentration-time curves and first-pass metabolism that would result from oral vs. intravenous ethanol. This model accurately predicted reported differences in AUC after oral vs. intravenous ethanol. First-pass metabolism has been shown to disappear when the stomach is bypassed via intraduodenal or portal vein infusion of ethanol. Our model predicts that the efficiency of first-pass metabolism is extremely sensitive to the hepatic delivery rate of ethanol and the rapid ethanol delivery rate in bypass studies would have eliminated hepatic first-pass metabolism. We conclude that hepatic ethanol 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 proposing that the gastric mucosa is the primary site of first-pass ethanol metabolism.