Studies on the Metabolic Fate of Felodipine (V): Absorption, Distribution, Metabolism and Excretion after a Single Oral Administration to Dogs

The absorption, distribution, metabolism and excretion of radioactivity were investigated after a single oral administration of 14C-felodioine 1 mg/kg to does of both sexes. 1. Radioactivity concentration in the plasma of male dogs reached a Cmax of 2, 228ng eq./ml at 2hr and then declined with half-lives of 4.8hr up to 8hr, 16hr from 12hr to 48hr and 123hr from 72hr to 168hr after administration. Radioactivity concentrations in the blood were 51 ?? 62% of those in the plasma. The AUC0-∞ was 41.3μg•eq. hr•ml-1. Profiles of radioactivity concentrations in the blood and plasma of female dogs were similar to those in male dogs. 2. In male dogs, 54.9 and 41.4% of the dose was excreted in the urine and feces within 168hr, respectively. In female dogs, 55.8 and 38.9% of the dose was excreted in the urine and feces within 168hr, respectively. The excretion of radioactivity was not sex dependent. 3. In the plasma, the parent compound was a minor substance and M-III and M-IV were mainly found. In the urine, M-III, M-IV and M-V were the major metabolites, while in the feces, M-III, M-IV, M-VI (lactone) and M-VII (lactone) were mainly found. Hardly any sex difference was present in the relative amounts of metabolites in the plasma, urine and feces. The major metabolites UM1 and UM2 found in the plasma of rats were not present in the plasma of dogs.