Studies on the Metabolic Fate of Felodipine (III):Absorption Site, Protein Binding, Distribution in Blood Cell, and Transfer into Fetus and Milk in Rats

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The distribution of radioactivity in fetuses and the transfer to milk were investigated after oral administration of ¹⁴C-Felodipine 1mg/kg to pregnant or lactating rats. Distribution in blood cells and the protein binding of radioactivity were also studied.
1. In a study of gastro-intestinal absorption in situ, the largest amount of ¹⁴C-Felodipine was rapidly absorbed from the small intestine, in addition, absorption also occured from the stomach and large intestine.
2. The distribution ratio of radioactivity in blood cells was less than 2% from 30min to 8hr after oral administration to male rats.
3. The protein binding ratios (in vitro) of radioactivity were over 99% in plasma samples of rats, dogs and human at 0.1 ?? 100μg/ml. The binding ratio (in vitro) of radioactivity to human albumin was 97%. In rats, the protein binding ratio (in vivo) of radioactivity was over 99%.
4. On the 12th and 18th days of gestation, the level of radioactivity in the fetus was lower than that in the maternal blood according to whole body autoradiograms. The level of radioactivity in the fetus on the 18th day of gestation was higher than that on the 12th day of gestation. On the 18th day of gestation, most of the fetal tissues showed maximum radioactivity concentrations 12hr after administration. The radioactivity concentrations in fetal tissues were less than 11% of that in the maternal plasma, the radioactivity concentration in brain being especially low. The disappearance of radioactivity from the fetal tissues was slightly slower than that from the maternal body.
5. The radioactivity concentration in milk was 6 ?? 13% of that in the plasma at any time.