Metabolic fate of a new dihydropyridine calcium antagonist, CD-349, in rat and dog.
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.
Ogawa
N
N
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Mizuno
K
K
Fukushima
K
K
Suwa
T
T
Satoh
T
T
D000818:Animals; D001646:Bile / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002250:Carbon Radioisotopes; D004095:Dihydropyridines / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004285:Dogs; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D002250:Carbon Radioisotopes; D004095:Dihydropyridines; C054179:CD 349