Comparison of the pharmacokinetics and pharmacodynamics of perindopril, cilazapril and enalapril.

1. The pharmacokinetic and pharmacodynamic responses to enalapril, perindopril and cilazapril have been studied in essential hypertensives (2, 4 and 8 mg perindopril and 2.5 mg cilazapril, single dose and steady state) and normotensive volunteers (10 mg enalapril, single dose). 2. Plasma levels of the active diacid compounds reached similar peaks after single dose administration of the drugs. However, perindoprilat levels persisted for 5 days whereas cilazaprilat levels were not detectable beyond 12 h. 3. The higher levels of perindoprilat were associated with a greater inhibition of plasma angiotensin-converting enzyme (ACE) activity in both acute and steady state studies. 4. The potency of the active diacids in inhibiting plasma ACE activity was perindoprilat greater than cilazaprilat greater than enalaprilat. 5. There was a close relationship between plasma concentration, ACE inhibition and blood pressure decrease. Although both cilazapril and perindopril administration reduced blood pressure in hypertensive subjects, only perindopril exerted 24 h blood pressure control at the doses used.