title: Use of measurements of ethanol absorption from stomach and intestine to assess human ethanol metabolism.
abstract: Controversy exists concerning the site (stomach vs. liver) and magnitude of first-pass metabolism of ethanol. We quantitated gastric and total ethanol absorption rates in five male subjects and utilized these measurements to evaluate first-pass metabolism. Gastric emptying of ethanol (0.15 g/kg) was determined via a gamma camera and gastric absorption from the ratio of gastric ethanol to [14C]polyethylene glycol. Gastric absorption accounted for 30% and 10% of ethanol administered with food and water, respectively. With food, estimated gastric mucosal ethanol concentrations fell from 19 to 5 mM over 2 h. Calculations using these concentrations and kinetic data for gastric alcohol dehydrogenase showed <2% of the dose underwent gastric metabolism. Application of observed ethanol absorption rates to a model of human hepatic ethanol metabolism indicated that only 30% and 4% of the dose underwent first-pass metabolism when administered with food and water, respectively. We conclude that virtually all first-pass ethanol metabolism occurs in the liver and first-pass metabolism accounts for only a small fraction of total clearance.
authors.affiliation: Research Service, Minneapolis Veterans Affairs Medical Center, Minnesota 55417, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Levitt
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.forename: E G
authors.initials: EG
authors.lastname: DeMaster
authors.forename: M
authors.initials: M
authors.lastname: Elson
authors.forename: J
authors.initials: J
authors.lastname: Furne
authors.forename: D G
authors.initials: DG
authors.lastname: Levitt
mesh_terms: D000042:Absorption; D000328:Adult; D002250:Carbon Radioisotopes; D004435:Eating; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics*; D005215:Fasting; D005746:Gastric Emptying; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D012016:Reference Values; D013270:Stomach / Q000000981:diagnostic imaging / Q000502:physiology*; D016284:Technetium Tc 99m Pentetate
chemical_list: D002250:Carbon Radioisotopes; D000431:Ethanol; D011092:Polyethylene Glycols; D016284:Technetium Tc 99m Pentetate