title: Inhibition of gastric alcohol dehydrogenase activity by histamine H2-receptor antagonists has no influence on the pharmacokinetics of ethanol after a moderate dose.
abstract: Ethanol undergoes gastric first pass metabolism by alcohol dehydrogenase (ADH). We have shown that cimetidine and famotidine both cause competitive inhibition of human gastric ADH in vitro. However, in a randomized 4-way cross-over study in 12 healthy subjects a 7-day course of treatment with cimetidine (800 mg day-1), ranitidine (300 mg day-1) or famotidine (40 mg day-1), did not modify the pharmacokinetics of ethanol given as a post-prandial 0.3 g kg-1 dose. We conclude that gastric mucosal concentrations of histamine H2-receptor blockers achieved after oral dosing are probably too low to cause significant inhibition of gastric ADH in vivo.
authors.affiliation: Service d'Hépatologie et de Gastroentérologie, Hôpital Henri Mondor, Créteil, France.
authors.forename: A
authors.initials: A
authors.lastname: Mallat
authors.forename: F
authors.initials: F
authors.lastname: Roudot-Thoraval
authors.forename: J F
authors.initials: JF
authors.lastname: Bergmann
authors.forename: H
authors.initials: H
authors.lastname: Trout
authors.forename: G
authors.initials: G
authors.lastname: Simonneau
authors.forename: C
authors.initials: C
authors.lastname: Dutreuil
authors.forename: L E
authors.initials: LE
authors.lastname: Blanc
authors.forename: D
authors.initials: D
authors.lastname: Dhumeaux
authors.forename: J C
authors.initials: JC
authors.lastname: Delchier
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000704:Analysis of Variance; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015738:Famotidine / Q000008:administration & dosage / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011899:Ranitidine / Q000494:pharmacology
chemical_list: D006635:Histamine H2 Antagonists; D000431:Ethanol; D015738:Famotidine; D002927:Cimetidine; D011899:Ranitidine; D000426:Alcohol Dehydrogenase