TY - JOUR T1 - Comparative metabolic disposition of oral doses of omeprazole in the dog, rat, and mouse. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 336 LP - 340 VL - 14 IS - 3 AU - K J Hoffmann AU - L Renberg AU - S G Olovson Y1 - 1986/05/01 UR - http://dmd.aspetjournals.org/content/14/3/336.abstract N2 - The metabolic disposition of [14C]omeprazole was studied in dogs, rats, and mice after the administration of pharmacologically active, single oral doses of drug in buffer solutions (pH 9). Averages of 38% (dogs), 43% (rats), and 55% (mice) of the radiolabeled doses were excreted in the urine in 72 hr. Most of the remaining dose was recovered in the feces. Omeprazole was extensively metabolized in all species studied and the metabolites were eliminated rapidly. No unchanged drug could be detected in the urine samples (less than 0.1% of dose). In each species at least 10 metabolites were detected in urine (pH 9) by gradient elution reverse phase HPLC. Based on liquid chromatographic retention data, the metabolic patterns were very complex and exhibited some quantitative differences between species. Bile was collected from rats and from chronic bile-fistulated dogs. Biliary excretion was a major route of elimination of omeprazole metabolites, and four polar metabolites were detected in the rat bile. The stability of omeprazole metabolites at varying pH values is discussed with reference to reductive metabolism of the parent compound. ER -