Clinical pharmacology of perindopril

Perindopril is a non-sulphydryl, pro-drug, ACE inhibitor. Following oral dosing, peak concentrations of the active moiety, perindoprilat, are achieved after 2-3 hours and perindoprilat is barely detectable by 24 hours. In contrast, maximal ACE inhibition is observed 4-6 hours after oral dosing and substantial inhibition persists beyond 24 hours. Inhibition of ACE is dose-dependent over the range 1-16 mg perindopril orally, and is mirrored by elevation of plasma renin activity and falls in aldosterone concentrations. Blood pressure reductions have been confirmed in normotensive and hypertensive subjects with maximal effect 6-10 hours after dosing and adequate antihypertensive activity at 24 hours. Blood pressure reductions are greater in the elderly than in young subjects due to pharmacokinetic differences. Dose reduction is required in elderly subjects and those with renal impairment. The antihypertensive efficacy of perindopril 4-8 mg once daily, is comparable to that of atenolol 50-100 mg once daily, captopril 25-50 mg twice daily or a hydrochlorothiazide/amiloride combination. Reduction in heart failure severity has also been reported. Perindopril appears to be a safe and effective agent for use in hypertension.