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.
Levitt
M D
MD
Research Service, Veterans Affairs Medical Center, Minneapolis, Minnesota.
Levitt
D G
DG
D000431:Ethanol / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D011169:Portal Vein
D000431:Ethanol