A pharmacokinetic study of cilazapril in patients with congestive heart failure.

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)