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  • Title: Metabolic fate of a new dihydropyridine calcium antagonist, CD-349, in rat and dog.
    Author: Ogawa N, Mizuno K, Fukushima K, Suwa T, Satoh T.
    Journal: Xenobiotica; 1993 Jul; 23(7):747-59. PubMed ID: 8237057.
    Abstract:
    1. The metabolic fate of 14C-CD-349, a new calcium antagonist, was studied in rat and dog. 2. After oral administration of 14C-labelled drug in both species, the plasma levels of radioactivity reached maxima at 1-2 h and declined with elimination half-lives of 6-7 h. In both species, 71-85% of radioactivity was excreted in faeces and 17-27% in urine in 120 h. Biliary excretion in rat after oral doses amounted to 33%. 3. The low ratio of unchanged drug to total radioactivity in plasma suggested that CD-349 underwent rapid metabolism in both species. 4. Twenty-two metabolites were isolated and identified from dog urine and an incubation mixture with 9000 g rat liver supernatant. Principal routes of biotransformation of CD-349 were similar in both species, and involved: (1) oxidation of the dihydropyridine ring to the corresponding pyridine ring; (2) denitration of the nitrate ester; (3) hydrolysis of the carboxy ester to the carboxylic acid; and/or (4) oxidation of the side chain, although quantitative interspecies differences were observed.
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