PT  - JOURNAL ARTICLE
AU  - William H. Schaefer
AU  - James Politowski
AU  - Bruce Hwang
AU  - Frank Dixon, Jr.
AU  - Anne Goalwin
AU  - Louis Gutzait
AU  - Kathleen Anderson
AU  - Charles DeBrosse
AU  - Mark Bean
AU  - Gerald R. Rhodes
TI  - Metabolism of Carvedilol in Dogs, Rats, and Mice
DP  - 1998 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 958--969
VI  - 26
IP  - 10
4099  - http://dmd.aspetjournals.org/content/26/10/958.short
4100  - http://dmd.aspetjournals.org/content/26/10/958.full
SO  - Drug Metab Dispos1998 Oct 01; 26
AB  - The excretion and biotransformation of carvedilol [1-[carbazolyl-(4)-oxy]-3-[(2-methoxyphenoxyethyl)amino]-2-propanol], a new, multiple-action, neurohormonal antagonist that exhibits the combined pharmacological activities of β-adrenoreceptor antagonism, vasodilation, and antioxidation, were investigated in dogs, rats, and mice. Carvedilol was absorbed well, and biliary secretion was predominant in each species. Carvedilol was metabolized extensively in each species, and elimination of unchanged compound was minor in bile duct-catheterized rats and dogs. In dogs, glucuronidation of the parent compound and hydroxylation of the carbazolyl ring, with subsequent glucuronidation, were the major metabolic pathways. Rats showed the simplest metabolite profile; the primary metabolites were formed by hydroxylation of the carbazolyl ring, with subsequent glucuronidation. Mice displayed the most complicated metabolite profile; glucuronidation of the parent compound and hydroxylation of either the carbazolyl or phenyl ring, with subsequent glucuronidation, were the major metabolic routes. O-Dealkylation was a minor pathway in all species examined. The American Society for Pharmacology and Experimental Therapeutics