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  • Title: Absorption, distribution, metabolism and excretion of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)- 1,4-dihydropyridine (PP-1466) in rats.
    Author: Inoue Y, Nakayama K, Wachi M, Kumakura K, Matsumoto T, Iwamoto M, Motoyoshi Y, Aikawa K.
    Journal: Arzneimittelforschung; 1985; 35(5):813-8. PubMed ID: 4026905.
    Abstract:
    In this experiment, the absorption, excretion, distribution and metabolism of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1, 4-dihydropyridine (PP-1466) were investigated following oral or intravenous administration, single dose or repeated dose administration using male SLC-Wistar rats and the results of this investigation were summarized as follows: After oral administration of 14C-PP-1466 to rats, the blood level reached the maximum at 1 h and decreased with the biological half-life of about 5 h. The unchanged drug concentration in plasma was 30% of total concentration in plasma and disappeared at 6 h. The high radioactivities in the liver, kidney, fat, lung and adrenal gland were observed after oral and intravenous administration. After oral and intravenous administrations, the excretion in feces and urine during 48 h was 63.0 and 32.4, 58.6 and 41.6%, respectively. Biliary excretion amounted to 57.6 and 46.2% during 48 h, respectively. Six metabolites were found in the urine of rats. Three of them were identified as 2,6-dimethyl-3-carbomethoxy-4-(2-difluoromethoxyphenyl)-5-carboxylic acid pyridine, 2-methyl-3-carbomethoxy-4-(2-difluoromethoxyphenyl)-5-carboxylic acid-6-hydroxymethyl pyridine and its lactonizing analogue. These three metabolites covered 54% of total urinary metabolites. After oral repeated administration for three weeks, the excretion ratio of radioactivity in urine and feces was constant during the administration and no accumulation was observed in rat tissues.
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