First pass metabolism of ethanol.
The human stomach has both low and high K(m) ADH isozymes, resulting in significant ethanol metabolism in gastric cells in vitro, and decreased bioavailability of ethanol (first pass metabolism: FPM) in vivo. Intraduodenal or intraportal infusion of amounts of ethanol equivalent to those emptied into the duodenum or disappearing from pylorus-ligated stomachs produced significantly higher blood levels than intragastric administration, whereas portal ligation had no effect, documenting the role of gastric ethanol metabolism in vivo. This "protective barrier" against the systemic effects of ethanol disappears after gastrectomy and is partly lost in the alcoholic because of accelerated gastric emptying and decreased gastric ADH activity, respectively. The latter is also lower in women than in men, at least below the age of 50. Some ADH isozymes require a relatively high ethanol concentration for optimal activity; therefore, the concentration of alcoholic beverages affects the amount metabolized. Fasting strikingly decreases FPM, most likely because of accelerated gastric emptying, resulting in shortened exposure of ethanol to gastric ADH and its more rapid intestinal absorption. Commonly used drugs, such as aspirin, acetaminophen and some H2-blockers decrease gastric ADH activity in vitro and produce increased blood alcohol levels in vivo, particularly at a low alcohol dose, equivalent to social drinking. Effects at higher ethanol dosage are still the subject of controversy. However, not all subjects display significant FPM, and published negative reports with H2 blockers do not specify whether first pass metabolism was present to begin with; some of the negative investigations also used dilute concentrations of alcohol, shown to minimize gastric metabolism. Thus, the stomach can metabolize amounts of ethanol of clinical relevance, an effect which is attenuated by various drugs, resulting in increased blood levels.
Lieber
C S
CS
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, NY, USA.
Gentry
R T
RT
Baraona
E
E
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000097:blood / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D008297:Male
D004791:Enzyme Inhibitors; D006635:Histamine H2 Antagonists; D007527:Isoenzymes; D000431:Ethanol; D000426:Alcohol Dehydrogenase