Metabolic fate of the new cardiotonic denopamine in animals. 4th communication: effects of coadministered drugs on the plasma concentration and metabolism of denopamine in dogs.

Effect of coadministered drugs on plasma level and metabolism of (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol (denopamine, TA-064), a new, orally active, cardiotonic agent, were studied in dogs. Plasma levels of denopamine and urinary excretion of denopamine and its main metabolites were determined after oral administration of denopamine with or without digoxin, furosemide and isosorbide dinitrate. Mean plasma levels of denopamine were slightly lower when denopamine was given with the coadministered drugs than when given alone, but the difference was not statistically significant. No significant differences were also found between the areas under the plasma concentration curve (110 vs. 127 ng/ml X h, with and without the coadministered drugs, respectively), peak plasma concentrations (32.4 vs. 39.6 ng/ml), times to peak concentration (1.2 vs. 1.0 h) and plasma half-lives (2.2 vs. 2.0 h), respectively. In addition, the urinary excretion of denopamine and its main metabolites was not affected by the coadministered drugs.