Abstract
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 andS-adenosylmethionine in vitro. These findings indicate that formation of 3-O-methyldobutamine constitutes a major pathway of dobutamine metabolism in humans.
Footnotes
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This study was supported in part by National Institute of Child Health and Human Development (Bethesda, MD) Grant 1 V10 HD 31313 (Network of Pediatric Pharmacology Research Units) to J.L.B.
- Abbreviations used are::
- COMT
- catechol-O-methyltransferase
- SAM
- S-adenosylmethionine
- HPLC
- high-performance liquid chromatography
- HPLC-EC
- high-performance liquid chromatography with electrochemical detection
- SULT
- sulfotransferase
- Received September 25, 2001.
- Accepted January 19, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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