Abstract
In a double-blind, placebo controlled, crossover study 12 patients with essential hypertension received single doses of 5, 10 and 20 mg of cilazapril, a new angiotensin converting enzyme (ACE) inhibitor. All doses similarly and significantly (P less than 0.05) reduced supine and erect blood pressure without increasing heart rate. The hypotensive effect was evident within 1 h, maintained for up to 8 h, with a maximal effect at 6 h. There was no discernible effect on blood pressure at 24 h after dosing. Plasma ACE activity was markedly inhibited to the same extent after all doses, with a peak inhibition of 94-96% at 2-3 h. At 24 h residual inhibition of ACE was 49-54%. Plasma renin activity increased in a dose-dependent manner with a peak at 6 h, and returned to baseline at 24 h. No correlation was found between the reduction in blood pressure and plasma renin activity, either at baseline or following cilazapril. There were no significant changes in plasma noradrenaline and the responses to upright posture and to dynamic exercise were preserved. There was no evidence of impaired exercise performance. Cilazapril is a potent ACE inhibitor with a rapid onset and a prolonged duration of action. These results suggest that peak ACE inhibition is achieved by 5 mg and that lower doses may be useful in clinical practice.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ajayi A. A., Campbell B. C., Howie C. A., Reid J. L. Acute and chronic effects of the converting enzyme inhibitors enalapril and lisinopril on reflex control of heart rate in normotensive man. J Hypertens. 1985 Feb;3(1):47–53. doi: 10.1097/00004872-198502000-00008. [DOI] [PubMed] [Google Scholar]
- Ajayi A. A., Campbell B. C., Meredith P. A., Kelman A. W., Reid J. L. The effect of captopril on the reflex control heart rate: possible mechanisms. Br J Clin Pharmacol. 1985 Jul;20(1):17–25. doi: 10.1111/j.1365-2125.1985.tb02793.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ajayi A. A., Hockings N., Reid J. L. Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat. Br J Clin Pharmacol. 1986 Apr;21(4):349–357. doi: 10.1111/j.1365-2125.1986.tb05206.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Campbell B. C., Sturani A., Reid J. L. Evidence of parasympathetic activity of the angiotensin converting enzyme inhibitor, captopril, in normotensive man. Clin Sci (Lond) 1985 Jan;68(1):49–56. doi: 10.1042/cs0680049. [DOI] [PubMed] [Google Scholar]
- Case D. B., Atlas S. A., Laragh J. H., Sullivan P. A., Sealey J. E. Use of first-dose response or plasma renin activity to predict the long-term effect of captopril: identification of triphasic pattern of blood pressure response. J Cardiovasc Pharmacol. 1980 Jul-Aug;2(4):339–346. doi: 10.1097/00005344-198007000-00001. [DOI] [PubMed] [Google Scholar]
- Chiknas S. G. A liquid chromatography-assisted assay for angiotensin-converting enzyme (peptidyl dipeptidase) in serum. Clin Chem. 1979 Jul;25(7):1259–1262. [PubMed] [Google Scholar]
- Da Prada M., Zürcher Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci. 1976 Oct 15;19(8):1161–1174. doi: 10.1016/0024-3205(76)90251-4. [DOI] [PubMed] [Google Scholar]
- Derkx F. H., Wenting G. J., Man in 't Veld A. J., Verhoeven R. P., Schalekamp M. A. Control of enzymatically inactive renin in man under various pathological conditions: implications for the interpretation of renin measurements in peripheral and renal venous plasma. Clin Sci Mol Med. 1978 May;54(5):529–538. doi: 10.1042/cs0540529. [DOI] [PubMed] [Google Scholar]
- Gavras H., Brunner H. R., Turini G. A., Kershaw G. R., Tifft C. P., Cuttelod S., Gavras I., Vukovich R. A., McKinstry D. N. Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man. N Engl J Med. 1978 May 4;298(18):991–995. doi: 10.1056/NEJM197805042981803. [DOI] [PubMed] [Google Scholar]
- McKenzie J. K., Clements J. A. Simplified radioimmunoassay for serum aldosterone utilizing increased antibody specificity. J Clin Endocrinol Metab. 1974 Apr;38(4):622–627. doi: 10.1210/jcem-38-4-622. [DOI] [PubMed] [Google Scholar]
- Millar J. A., Derkx F. H., McLean K., Reid J. L. Pharmacodynamics of converting enzyme inhibition: the cardiovascular, endocrine and autonomic effects of MK421 (enalapril) and MK521. Br J Clin Pharmacol. 1982 Sep;14(3):347–355. doi: 10.1111/j.1365-2125.1982.tb01990.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Natoff I. L., Nixon J. S., Francis R. J., Klevans L. R., Brewster M., Budd J., Patel A. T., Wenger J., Worth E. Biological properties of the angiotensin-converting enzyme inhibitor cilazapril. J Cardiovasc Pharmacol. 1985 May-Jun;7(3):569–580. doi: 10.1097/00005344-198505000-00025. [DOI] [PubMed] [Google Scholar]
- Niarchos A. P., Pickering T. G., Morganti A., Laragh J. H. Plasma catecholamines and cardiovascular responses during converting enzyme inhibition in normotensive and hypertensive man. Clin Exp Hypertens A. 1982;4(4-5):761–789. doi: 10.3109/10641968209061612. [DOI] [PubMed] [Google Scholar]
- Sturani A., Chiarini C., Degliesposti E., Santoro A., Zuccalà A., Zucchelli P. Heart rate control in hypertensive patients treated by captopril. Br J Clin Pharmacol. 1982 Dec;14(6):849–855. doi: 10.1111/j.1365-2125.1982.tb02048.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waeber B., Brunner H. R., Brunner D. B., Curtet A. L., Turini G. A., Gavras H. Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril. Hypertension. 1980 Mar-Apr;2(2):236–242. doi: 10.1161/01.hyp.2.2.236. [DOI] [PubMed] [Google Scholar]
- Zanella M. T., Bravo E. L., Fouad F. M., Tarazi R. C. Long-term converting enzyme inhibition and sympathetic nerve function in hypertensive humans. Hypertension. 1981 Nov-Dec;3(6 Pt 2):II–216-21. doi: 10.1161/01.hyp.3.6_pt_2.ii-216. [DOI] [PubMed] [Google Scholar]