Studies on the metabolic fate of Benazepril hydrochloride in rats II: Plasma level profile, distribution, metabolism and excretion after repeated oral administration.

Abstract

The absorption, distribution, metabolism and excretion of 14C-CGS 14824 A were studied in male rats durine and after 21 day consecutive oral administration of 3mg/kg/day. 1. The plasma radioactivity at 30min and 8hr after each dose was not affected by repeated administration. The radioactivity in the plasma reached Cmax of 789ng eq./ml (20min) and 987ng eq./ml (30min) after the 1st and 21st doses, respectively. After reaching peak concentration, half-lives were similar between the 1st and 21st administration. 2. The radioactivity in tissues at 6hr was not significantly different after the 7th, 14th and 21st doses and 1st dose. After the final administration, high levels of radioactivity were observed in the gastrointestinal tract, liver, bladder and lung. Elimination of radioactivity from tissues was rapid and no accumulation of radioactivity in tissues was observed. 3. The extent of excretion in urine and feces during concecutive oral administration was about 35% and 65%, respectively. The elimination of radioactivity from the body was completed 48hr after the final administration. 4. After repeated oral administration to non-fasting male rats, the radioactivity in the plasma, lung, liver and kidney mainly corresponded to CGS 14831. In the urine and feces, the composition was similar.