Abstract
1 Cilazaprilat is an inhibitor of angiotensin converting enzyme (ACE) and is the active metabolite of cilazapril. The pharmacokinetics of cilazaprilat, and the inhibition of plasma ACE were investigated in 12 elderly and 12 young healthy volunteers.
2 Single oral 1 mg doses of cilazapril were given to the elderly (age range 65-83 years) and the young (age range 18-31 years) in an open study. Plasma and urinary cilazaprilat concentrations, and plasma ACE activities were measured up to 72 h after dosing by radioenzymatic methods.
3 Cilazapril was well tolerated in both young and elderly subjects. Small falls in blood pressure were observed up to 8-24 h after dosing.
4 The mean peak plasma cilazaprilat concentration in the elderly (11.5 ng ml-1) was significantly greater (P < 0.02) than the corresponding value in the young (8.3 ng ml-1). Total and renal clearances were significantly lower (both P < 0.05) in the elderly (12.8 and 5.11 h-1) than in the young (16.0 and 7.21 h-1). Total urinary recovery of cilazaprilat was similar for the two groups at about 43% of dose.
5 Plasma ACE inhibition was slightly greater in the elderly but the mean inhibition in the two groups did not differ by more than 10% at any time-point from 1-72 h.
6 The plasma concentrations of cilazaprilat required for 90% ACE inhibition were similar at 4.7 and 4.8 ng ml-1 in the elderly and young respectively.
7 It is concluded that the age-related changes in cilazaprilat kinetics and in the degree of ACE inhibition are small. On their own, these changes do not imply a need for reduced dosage in the elderly but further clinical experience will help to establish a suitable dosage regimen of cilazapril for elderly hypertensives.
Keywords: cilazapril, cilazaprilat, pharmacokinetics, elderly, ACE
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Creasey W. A., Funke P. T., McKinstry D. N., Sugerman A. A. Pharmacokinetics of captopril in elderly healthy male volunteers. J Clin Pharmacol. 1986 Apr;26(4):264–268. doi: 10.1002/j.1552-4604.1986.tb03521.x. [DOI] [PubMed] [Google Scholar]
- Francis R. J., Brown A. N., Kler L., Fasanella d'Amore T., Nussberger J., Waeber B., Brunner H. R. Pharmacokinetics of the converting enzyme inhibitor cilazapril in normal volunteers and the relationship to enzyme inhibition: development of a mathematical model. J Cardiovasc Pharmacol. 1987 Jan;9(1):32–38. [PubMed] [Google Scholar]
- Gautam P. C., Vargas E., Lye M. Pharmacokinetics of lisinopril (MK521) in healthy young and elderly subjects and in elderly patients with cardiac failure. J Pharm Pharmacol. 1987 Nov;39(11):929–931. doi: 10.1111/j.2042-7158.1987.tb03130.x. [DOI] [PubMed] [Google Scholar]
- Greenblatt D. J., Sellers E. M., Shader R. I. Drug therapy: drug disposition in old age. N Engl J Med. 1982 May 6;306(18):1081–1088. doi: 10.1056/NEJM198205063061804. [DOI] [PubMed] [Google Scholar]
- Hockings N., Ajayi A. A., Reid J. L. Age and the pharmacokinetics of angiotensin converting enzyme inhibitors enalapril and enalaprilat. Br J Clin Pharmacol. 1986 Apr;21(4):341–348. doi: 10.1111/j.1365-2125.1986.tb05205.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meyer B. H., Müller F. O., Badian M., Eckert H. G., Hajdú P., Irmisch R., Schmidt D. Pharmacokinetics of ramipril in the elderly. Am J Cardiol. 1987 Apr 24;59(10):33D–37D. doi: 10.1016/0002-9149(87)90050-6. [DOI] [PubMed] [Google Scholar]
- Nussberger J., Fasanella d'Amore T., Porchet M., Waeber B., Brunner D. B., Brunner H. R., Kler L., Brown A. N., Francis R. J. Repeated administration of the converting enzyme inhibitor cilazapril to normal volunteers. J Cardiovasc Pharmacol. 1987 Jan;9(1):39–44. [PubMed] [Google Scholar]
- Rakhit A., Kochak G. M., Tipnis V., Radensky P., Hurley M. E., Williams R. Pharmacokinetics of pentopril in the elderly. Br J Clin Pharmacol. 1987 Sep;24(3):351–357. doi: 10.1111/j.1365-2125.1987.tb03180.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ryan J. W., Chung A., Ammons C., Carlton M. L. A simple radioassay for angiotensin-converting enzyme. Biochem J. 1977 Nov 1;167(2):501–504. doi: 10.1042/bj1670501. [DOI] [PMC free article] [PubMed] [Google Scholar]