FIRST PASS METABOLISM OF ETHANOL: GASTRIC OR men by starch gel electrophoresis and by comparing the reduction of m-nitrobenzaldehyde (a preferred sub-HEPATIC, MOUNTAIN OR MOLEHILL strate of s-ADH) and the glutathione-dependent formal-Ammon E, Scha ¨fer C, Hoffmann U, Klotz U. Disposition dehyde oxidation (a specific reaction of x-ADH). Alcohol and first pass metabolism of ethanol in humans: is it gastric pharmacokinetics was compared in 10 Japanese and 10 or hepatic and does it depend on gender? Reprinted with Caucasians after administration of ethanol (300 mg/kg permission. Clin Pharmacol Ther 1996;59:503-513. of body weight) intravenously or orally, using 5% and 40% oral solutions. Japanese exhibited lower s-ADH ac-ABSTRACT tivity than Caucasians, with no difference in the other gastric isozymes. With 5% ethanol, first-pass metabolism The objective of the study was to assess the extent was strikingly lower in Japanese than in Caucasians. and site of the first-pass metabolism of ethanol and to Blood alcohol levels were similar because of the high examine whether first-pass metabolism and disposition elimination rate in Japanese due to the hepatic b 2 -ADH of ethanol are dependent on gender. After a standardvariant. With 40% ethanol, the first-pass metabolism inized lunch, healthy subjects (six women and six men) creased in both groups to comparable levels, suggesting received on two separate occasions a 60-minute intravean additional contribution by x-ADH at high ethanol nous infusion of ethanol (0.3 gm/kg) and concomitantly concentrations. These results indicate that s-ADH activan equimolar dose of d 3 -ethanol/kg either orally (over 20 ity contributes significantly to gastric ethanol oxidation minutes) or intraduodenally (infused over 30 minutes). and its lower activity in Japanese is associated with Blood levels, urinary excretion of d 0 -and d 3 -ethanol, and lesser first-pass metabolism. sedative effects were monitored for 6 hours. Disposition and first-pass metabolism of ethanol were evaluated by COMMENTS