DISPOSITION OF DOBUTAMINE IN DOG

Abstract

The disposition of dobutamine, a potent inotropic catecholamine, was examined in the dog. A sensitive assay was developed for dobutamine, allowing the measurement of the drug at plasma concentrations as low as 1 ng/ml. The short plasma half-life of dobutamine (1-2 min) was due to rapid redistribution of dobutamine from the plasma to the tissue. When 14C-dobutamine was administered, the plasma half-life of radioactivity was 1.9 h. The circulating radioactivity consists mainly of the glucuronide conjugate of 3-O-methyldobutamine. During continuous i.v. administration of dobutamine, plasma levels of metabolites reached a maximum between 3 and 4 h. During a 48 h time period after administration of 14C-dobutamine, 67% of the radiolabel was excreted in the urine and 20% in the feces. In dogs having cannulated bile ducts, 30-35% of the administered drug was excreted in the bile. The major urinary metabolites were the glucuronide conjugates of dobutamine and 3-O-methyldobutamine.