PT - JOURNAL ARTICLE AU - S Furuuchi AU - K Naito AU - M Otsuka AU - S Harigaya TI - Metabolism of denopamine, a new cardiotonic agent, in the rat and dog. DP - 1985 Sep 01 TA - Drug Metabolism and Disposition PG - 620--626 VI - 13 IP - 5 4099 - http://dmd.aspetjournals.org/content/13/5/620.short 4100 - http://dmd.aspetjournals.org/content/13/5/620.full SO - Drug Metab Dispos1985 Sep 01; 13 AB - The metabolism of denopamine, (R)-(-)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino] ethanol, a new, orally active, selectively inotropic cardiotonic agent, was studied in the rat and dog. Animals were given single oral doses of 5 mg/kg of denopamine labeled with 14C. Denopamine was metabolized in the rat and dog by several pathways including conjugation, side chain oxidation, and ring hydroxylation followed by O-methylation. Rats excreted the drug in the urine almost entirely as unchanged drug and its phenolic O-glucuronide whereas in the dog, the major metabolites were the phenolic O-glucuronide, the alcoholic O-glucuronide, and the phenolic O-sulfate of denopamine and the phenolic O-glucuronide of 3-methoxydenopamine. Demethylation, which has been shown to be a major metabolic pathway in man, and side chain oxidation were minor pathways in the rat and dog. Furthermore, a high degree of stereoselective resistance of the alcoholic O-glucuronide of denopamine to hydrolysis by beta-glucuronidase was observed.