Pharmacokinetics of single and consecutive doses of cilazapril and its depressor effects in patients with essential hypertension.

The pharmacokinetic properties and antihypertensive effects of cilazapril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, were investigated in five patients with mild to moderate essential hypertension (mean age 57 years, mean serum creatinine 1.2 mg/dL, mean glomerular filtration rate 69 mL/min/1.73m2, mean blood pressure 158/94 mm Hg). All patients were hospitalized and placed on a constant sodium diet (7 g of NaCl/day) throughout the study. After an overnight fast, a 1.25-mg dose of cilazapril was given orally once a day for 5 or 8 days. On the first and last days of treatment, blood samples were taken and blood pressure was measured. All patients tolerated cilazapril with no untoward effects. Cilazapril induced a significant decrease in both systolic and diastolic blood pressure, and its antihypertensive effect was still present 24 hours after administration. Serum ACE activity was markedly suppressed for at least 24 hours. The peak plasma concentrations (Cmax) of cilazapril and its diacid were 117 and 24.6 ng/mL on the first treatment day, and 144 and 31.1 ng/mL on the last day. The area under the plasma concentration time curve (AUC) of cilazapril and its diacid were 408 and 227 ng.h/mL on the first day, and 501 and 305 ng.h/mL on the last day. In looking at the data gathered on the first and last treatment days, no significant differences were noted in Cmax and AUC values. These results suggest that cilazapril has a long-lasting effect and is a useful antihypertensive agent in controlling blood pressure in patients with mild to moderate essential hypertension.