Experience with perindopril in normal volunteers

The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril was evaluated in normotensive men. Doses of 2 to 16 mg were given once a day for up to one week. Single oral doses of perindopril were found to blunt the pressor response to exogenous angiotensin I in a dose-dependent manner. The drug-induced ACE inhibition, as estimated by the measurement of plasma ACE activity, was maximal 4 to 8 hours post drug intake. ACE activity was still importantly reduced 24 hours after dosing. Plasma levels of angiotensin II and aldosterone decreased significantly whereas plasma renin activity and blood angiotensin I levels rose during peak ACE inhibition induced by the 4 and 8 mg doses. However, circulating levels of angiotensin II returned to baseline 24 hours after dosing, both on the first day of treatment and after one week of administration. ACE inhibition with perindopril did not affect blood pressure and heart rate in any consistent manner. There was no evidence for drug accumulation during repeated administration. The novel ACE inhibitor was well tolerated and produced no change in routine laboratory tests. The long-acting ACE inhibitor perindopril appears therefore to be effective when given orally in a dose range of 4 to 16 mg.