3-O-methyldobutamine, a major metabolite of dobutamine in humans.
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 approximately 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.
Yan
Maohe
M
Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.
Webster
Leslie T
LT
Blumer
Jeffrey L
JL
D000318:Adrenergic beta-Agonists / Q000378:metabolism* / Q000652:urine; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002648:Child; D004280:Dobutamine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000652:urine; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D012436:S-Adenosylmethionine / Q000378:metabolism / Q000652:urine
D000318:Adrenergic beta-Agonists; D004280:Dobutamine; D012436:S-Adenosylmethionine; C044730:3-O-methyldobutamine; D002394:Catechol O-Methyltransferase