1. The pharmacokinetics of
cilazapril and the inhibition of
angiotensin converting enzyme (ACE) were investigated in 10 patients with
congestive heart failure, NYHA class II-III, receiving
diuretics with or without
digoxin. 2. Patients received 0.5 mg and 1 mg
cilazapril on the first 2 days, followed by 0.5 mg or 1 mg daily for the next 8 weeks, in a single-blind study. Plasma
cilazaprilat concentrations and plasma ACE activities were measured by radioenzymatic methods up to 24 h after the first and last doses. 3. After the initial 0.5 mg dose of
cilazapril, a mean maximum plasma concentration of
cilazaprilat of 6.8 ng ml-1 was observed at 2.3 h. Concentrations declined up to 8 h with a mean half-life of 5.8 h, followed by slower decrease to 24 h. Total clearance, based on data to 24 h, was estimated at 8.5 l h-1, with three-fold inter-individual variation. Mean maximum plasma ACE inhibition was 87%, decreasing to 65% at 24 h. 4. In the multiple dose phase of the study, four patients received
cilazapril 0.5 mg daily, and six patients 1 mg daily.
Cilazapril accumulation for the 0.5 mg group averaged 77%, but steady state concentrations for the 1 mg group were less than double those of the 0.5 mg group. ACE inhibition profiles at steady state were similar for both groups, and they differed from first dose data only in a somewhat lower inhibition at 24 h. 5. Historical comparison of the first-dose data with those for healthy young volunteers at identical dosage revealed only minor differences in kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)