Vol. 30, Issue 5, 519-524, May 2002

3-O-Methyldobutamine, a Major Metabolite of Dobutamine in Humans

Maohe Yan, Leslie T. Webster, Jr., and Jeffrey L. Blumer

Departments of Pediatrics and Pharmacology, Case Western Reserve University, Division of Pediatric Pharmacology and Critical Care, Rainbow Babies and Children's Hospital of the University Hospitals of Cleveland, Cleveland, Ohio

Dobutamine is a synthetic ionotropic catecholamine commonly used to treat heart failure and shock. The catabolic fate of dobutamine in humans has yet to be reported, although formation of 3-O-methyldobutamine represents the principal pathway of dobutamine disposition in the dog. Herein, we describe the isolation and identification of 3-O-methyldobutamine in the urine of children receiving infusions of racemic dobutamine. In a 9-year-old child with heart failure ~80% of dobutamine administered intravenously at steady state was detected in the urine. Forty-seven percent of infused dobutamine was identified as 3-O-methyldobutamine and its acid-hydrolyzed derivatives, the latter mostly conjugated with sulfate (33%). Thirty-two percent consisted of acid-hydrolyzed dobutamine metabolites, primarily conjugated with sulfate (16%). Sonicates of human blood mononuclear cells catalyzed the formation of 3-O-methyldobutamine from dobutamine and S-adenosylmethionine in vitro. These findings indicate that formation of 3-O-methyldobutamine constitutes a major pathway of dobutamine metabolism in humans.