Studies on the Pharmacokinetics of Perindopril Erbumine in Rats (2): Blood Level Profile, Distribution, Metabolism and Excretion after Repeated Oral Administration

Pharmacokinetic studies on blood level, tissue distribution, metabolism and excretion of perindopril erbumine, an ACE inhibitor, were performed in rats during and after repeated oral administration of 14C-perindopril erbumine (14C-DW-7950) at a daily dose of 0.5 mg/kg for 14 days. 1. The blood levels of radioactivity reached the steady state during 5 days and the Css (Cmin) on day 5 was 7.09 ng eq./ml at the accumulation factor of 1.1. 2. After repeated oral administration, the radioactivity was mainly distributed in lung, kidney, liver and intestinal tract. The radioactivity in the lung, in which higher ACE activity distributed, was the highest and reached the steady state during 14 days. Elimination of radioactivity from most of tissues was rapid. It is assumed that the accumulation of radioactivity in plexus chorioideus arose from high localization of ACE. 3. Excretion rate in urine and feces during repeated oral administration was almost constant. At 168 hr after the last dosing, the extent of excretion of radioactivity from the body was 33.1% and 69.6%, respectively. 4. After repeated oral administration, an active metabolite, perindoprilat, was found and accounted for most of radioactivity present in the plasma, lung, liver and kidney, and also in urine and feces.