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Cilazapril is a new angiotensin-converting enzyme (ACE) inhibitor. In a double-blind crossover study six normal male volunteers received single oral doses of cilazapril, 4 mg, captopril, 25 mg, enalapril, 10 mg, and placebo. The response of diastolic blood pressure to an intravenous infusion with increasing doses of angiotensin I (AT-I) (0.1 to 18 micrograms/min) was determined at control and up to 36 hours after oral drug intake. Additionally the response to AT-I was established before, during, and after cessation of a 15-day 2.5 mg/day cilazapril administration. The ACE inhibitors antagonized the AT-I effects and shifted the AT-I dose-effect curves rightward, whereas placebo was not effective. After single doses the effects of cilazapril and enalapril declined with a similar elimination half-life of approximately 4 hours; with captopril approximately 2 hours was observed. After multiple administration of cilazapril there was no evidence of cumulative effects. Cilazapril is an orally active ACE inhibitor that does not show pharmacodynamically relevant accumulation.

Dose‐response curves of the effect of angiotensin I (A‐I) infusion on diastolic blood pressure were constructed before and 3 h following single oral doses of the angiotensin‐converting enzyme (ACE) inhibitor cilazapril (1.25 to 30 mg) in six normal male subjects. Cilazapril shifted the A‐I dose‐response curves dose dependently rightward; Schild‐ plot analysis indicated a competitive antagonism by cilazapril with an apparent Ki‐dose of about 0.6 mg.

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1 The aim of the studies was to develop a new methodology to estimate the pharmacodynamic properties and potency of angiotensin converting enzyme (ACE) inhibitors in man. 2 Angiotensin I dose-response curves were derived by continuous infusion of angiotensin I in increasing dose steps; steady state was reached within 3 min. 3 Interaction between angiotensin I (agonist) and ACE inhibitors (antagonist) was characterized according to Schild-plot methodology by measuring agonist dose-response curves using diastolic blood pressure in the absence and the presence of varying doses of the antagonist. 4 Cilazapril shifted the angiotensin I dose-response curves to the right. A twofold shift (apparent K1-dose) was observed with approximately 0.6 mg cilazapril.5 The effect of angiotensin I on diastolic blood pressure was determined before and up to 36 h after administration of 25 mg captopril, 10 mg enalapril, 4 mg cilazapril and a placebo orally. The pharmacodynamic half-life of captopril was about 2 h, whereas the effect of enalapril and cilazapril was about 4 h. 6 Angiotensin I dose-response curves are useful methods of investigating the pharmacodynamic properties of ACE-inhibitors in man.