Pharmacokinetic studies on plasm a level, tissue distribution, metabolism and excretion of perindopril erbumine, an ACE inhibitor, were performed in fasting male rats after single oral administration of 14C-perindopril erbumine (14C-DW-7950) at a dose of 0.5 mg/kg.
1. The radioactivity in plasma reached the Cmax of 88 ng eq./ml at 1 hr and the elimination half-lives were 2.1 hr (2-8 hr) and 34 hr (24-72 hr).
2. After single oral administration, the radioactivity was rapidly distributed to tissues, reaching maximum levels at 1 hr in most tissues. At 8 hr, a high level of radioactivity was detected in the lung, pituitary gland, intestine, kidney and aorta, due to intensive localization of ACE in these tissues. At 168 hr, the level of radioactivity was reduced in all tissues.
3. The radioactivity was excreted within 168 hr into urine and feces at the rate of 39.7% and 58.7% of the dose, respectively. Biliary excretion of radioactivity was 31.2% within 48 hr. The total recoveries from urine, bile and carcass were 75.4% of dose, suggesting good gastrointestinal absorption.
4. After oral administration, an active metabolite, perindoprilat, was found and accounted for most of the total radioactivity in the plasma, lung, liver and kidney, and also in urine and feces.
5. In the study of dose-dependency, linear pharmacokinetics were observed.
