Antihypertensive effects and pharmacokinetics of single and consecutive doses of cilazapril in hypertensive patients with normal or impaired renal function.

1. A 1.25 mg dose of cilazapril, a new angiotensin-converting enzyme (ACE) inhibitor, was administered orally to two groups of hypertensive patients, five with normal renal function (NRF) and seven with impaired renal function (IRF), once daily for 5 or 8 consecutive days. Blood pressure, heart rate and serum ACE activity were measured up to 24 h following the initial and the last dose. Plasma level profiles of cilazapril and its active diacid were also evaluated on the first and the last day of treatment. 2. Cilazapril induced significant falls in both systolic and diastolic blood pressures without increasing heart rate. The antihypertensive effect was evident within 1 h after drug administration and was sustained for up to 24 h, particularly after consecutive dosing. 3. Serum ACE activity was markedly suppressed over 24 h. The recovery of ACE activity was delayed in the IRF group when compared with the NRF group. 4. Plasma concentrations of the active diacid in the IRF group were higher than in the NRF group with significant differences in the peak concentrations and area under the plasma concentration-time curve (AUC). The plasma concentration profile for the parent drug was similar for both the NRF and IRF groups. 5. A significant inverse correlation was found between the creatinine clearance and the AUC for the diacid. 6. Cilazapril is a potent ACE inhibitor with a prolonged duration of antihypertensive effect and is a useful agent for controlling blood pressure in hypertensives either with NRF or IRF. In patients with severe renal impairment the dose of cilazapril should be reduced.