1. It has been reported that calcium antagonists lower blood pressure more effectively in salt replete hypertensive patients with a low plasma renin activity (PRA), whereas angiotensin converting enzyme (ACE) inhibitors are more effective in salt depleted patients with a high level of PRA. An inverse relationship between the antihypertensive effects of these two groups of drugs might therefore be expected. 2. Since salt retention and inappropriately high levels of PRA are said to contribute to hypertension in patients with chronic renal failure (CRF), an additive antihypertensive effect with both drugs might also be expected in such patients. 3. To test these hypotheses, we investigated the acute and chronic antihypertensive effects of the calcium antagonist nitrendipine and the new ACE inhibitor cilazapril, given alone, and in combination, in a double‐blind, randomized, placebo controlled study of 11 hypertensive patients with chronic renal failure who had a mean pretreatment blood pressure of 149 +/‐ 3/96 +/‐ 2 mm Hg. Patients received nitrendipine 10 mg, cilazapril 1.25 or 2.5 mg depending on creatinine clearance, or placebo once daily orally. Nitrendipine and cilazapril were also combined at the same doses. 4. Nitrendipine and cilazapril were equally effective, with a maximal acute reduction of mean arterial pressure (MAP) of 5.3 +/‐ 1.8% and 8.0 +/‐ 1.9%, and after 1 week of treatment 5.0 +/‐ 2.4% and 8.1 +/‐ 1.8%, respectively. In individual patients no inverse relationship between the blood pressure responses to the two drugs was found.(ABSTRACT TRUNCATED AT 250 WORDS)

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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 < 40ml 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.