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1. The pharmacokinetic and pharmacodynamic properties of the angiotensin converting enzyme (ACE) inhibitor cilazapril were studied in 30 hypertensive patients with various degrees of renal function. 2. After a single oral dose, apparent cilazaprilat clearance was dependent on renal function being 16.0 +/- 3.0, 11.1 +/- 3.0, 8.7 +/- 3.7 and 6.7 +/- 2.1 l h-1 (means +/- s.d.) in patients with creatinine clearances (CLcr) of > 100, 41-100, 21-40, and 8-20 ml min-1, respectively. .3 During 11 weeks of treatment with cilazapril, doses were adjusted to the CLcr and varied from 0.5 to 5.0 mg once daily. At 24 h after drug administration a clear antihypertensive response was seen only in the low clearance groups (CLcr < 40 ml min-1). In contrast, and despite higher once daily dosages, the decline of mean arterial pressure was small and cilazaprilat concentrations after 24 h were lower in the high clearance groups. 4. This study demonstrates that chronic once daily treatment with cilazapril is effective in patients with impaired renal function at dosages adjusted to creatinine clearance. No accumulation was seen. Since cilazaprilat clearance was high in the high creatinine clearance groups, a clear antihypertensive response in these groups was only seen at 3 h after drug administration.

bjcp. british journal of clinical pharmacology/british journal of clinical pharmacology

Pharmacokinetics and haemodynamic effects of the angiotensin converting enzyme inhibitor cilazapril in hypertensive patients with normal and impaired renal function