Studies on the Metabolic Fate of Felodipine. (II): Absorption, Distribution, Metabolism and Excretion after Repeated Oral Administration to Rats.

Abstract

The absorption, distribution, metabolism, and excretion of 14C-Felodipine were investigated during and after its repeated oral administration to male rats at a daily dose of 1mg/kg for 28 days. 1. The concentration of radioactivity in the blood (24hr after daily dosing) almost reached a steady state after the 25th dosing and was 1.9 times higher after the 28th dosing than that found after the 1st dosing. The Cmax after the 28th dosing was 1.3 times higher than that in the single dosing. The half-life up to 48hr was 1.4 times longer and the half-life from 72hr to 168hr was 2.2 times longer than that found in the single dosing. 2. The excretion of radioactivity in the urine and feces reached almost a steady state by the 14th dosing. 3. Most of the tissues tended to reach a steady state by the 14th dosing. The disappearance of radioactivity after the 28th dosing was slower than that in the single dosing. The fractionation of radioactivity in the fat 168, 336 and 1, 008hr and liver 168hr after the 28th dosing suggested that radioactivity in the fat and liver was not due to the metabolites of Felodipine but due to the labelled carbon which is taken up by biological components. 4. The relative amounts of metabolites in the plasma and urine did not change with repeated dosing.