Antihypertensive Effects and Pharmacokinetics of Single and Consecutive Doses of Cilazapril in Hypertensive Patients with Normal and Impaired Renal Function

Summary: The antihypertensive effects and pharmacokinetic properties of cilazapril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, were investigated in hypertensive patients with normal renal function (NRF; n = 5) and those with impaired renal function (IRF; n = 7). A 1.25-mg dose of cilazapril was administered orally once a day for 5 or 8 days. Measurement of blood pressure and sampling of blood specimens were done on the first and last days of treatment. Cilazapril induced significant falls in systolic and diastolic blood pressures as early as 1 h after administration. The antihypertensive effects were still present at 24 h postdose. Serum ACE activity was markedly suppressed over 24 h, with the enzyme inhibition greater in the IRF group. Plasma levels of the active diacid in the IRF group were higher than those in the NRF group, with significant differences in the peak levels and areas under the curve (AUC). A significant inverse correlation was found between the creatinine clearance and the AUC for the diacid. Cilazapril was well tolerated by all the patients, and no adverse reactions were observed. These results suggest that cilazapril has a long-lasting action and that it is a useful antihypertensive agent for controlling blood pressure in patients with either NRF or IRF.