Inhibition of angiotensin-I response by cilazapril and its time course in normal volunteers.
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.
D000293:Adolescent; D000328:Adult; D000803:Angiotensin I / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D017315:Cilazapril; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004656:Enalapril / Q000494:pharmacology; D006801:Humans; D008297:Male; D011724:Pyridazines / Q000494:pharmacology*; D011897:Random Allocation; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; D004656:Enalapril; D000803:Angiotensin I; D002216:Captopril