Metabolic Fate of Carteolol Hydrochloride [5-(3-tert-butylamino-2-hydroxypropoxy)-3, 4-dihydrocarbostyril Hydrochloride, OPC-1085], a New β-Blocker. V. Identification of Metabolites in Rat, Dog and Human
The metabolism of carteolol hydrochloride was investigated in rats and dogs after oral administration of 14C-carteolol hydrochloride. The metabolites were identifed by gas chromatography-mass spectrometry. In the rat summation of radioactivity excreted in urine and feces during 48 h was about 35 and 62%, respectively. The major radioactive metabolites including glucuronides were carteolol (35%) and 8-hydroxycarteolol (47%) from urine, and carteolol (35%), 8-hydroxycarteolol (20%) and dihydroxycarteolol (33%) from feces. In the dog the summation of radioactivity excreted in urine and feces during 48 h was about 62% 27%, respectively. The major radioactive metabolites including glucuronides were carteolol (35%), 8-hydroxycarteolol (45%) and dihydroxycarteolol (9%) from urine, and carteolol (23%) and 8-hydroxycarteolol (61%) from feces. Carteolol and 8-hydroxycarteolol were also identified from human urine. The minor metabolites were identifed as 5-hydroxy-3,4-dihydrocarbostyril and 5,8-dihydroxy-3,4-dihydrocarbostyril from the rat and the dog, and as 5-carboxymethoxy-3,4-dihydrocarbostyril from dog urine. Antagonism of 8-hydroxycarteolol, the main metabolite, against the positive chromotropic and hypotensice actions of isoproterenol was examined in anesthetized dogs.