Abstract
Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum ACE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 μ·ml−1), and by 12 hours the compound had al most disappeared (67 ng·ml−1). Derived t1/2 was 1.4–2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol−1·min−1·ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 12 hours) pg·ml−1] for up to 12 h, while active renin rose up to 24 h [from 12.3 to 20.1 (after 8 hours) and 17.5 (after 24 hours) pg·ml−1]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg) up to 24 hours (idrapril calcium 142/91 mmHg; placebo: 155/97 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.
Similar content being viewed by others
References
Waeber B, Nussberger J, Brunner HR (1995) Angiotensin-converting enzyme inhibitors in hypertension. In: Hypertension: pathophysiology, diagnosis, and management, 2 edn. Laragh JH, Brenner BM (eds) Raven Press, New York, pp 2861–2875
Salvetti A (1990) Newer ACE inhibitors. A look at the future. Drugs 40:800–828
The Consensus Trial Study Group (1987) Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (Consensus). New Engl J Med 316:1429–1435
Turbanti L, Cerbai G, Di Bugno C, Giorgi R, Garzelli G, Criscuoli M, Renzetti AR, Subissi A, Bramanti G (1992) 1,2-Cyclomethylene-carboxylic monoamide hydroxamic derivatives. A novel class of non-aminoacid angiotensin converting enzyme Inhibitors. J Med Chem 36:699–707
Subissi A, Criscuoli M, Sardelli G, Guelfi M, Giachetti A (1992) Pharmacology of idrapril: a new class of angiotensin converting enzyme inhibitors. J Cardiovasc Pharmacol 20:139–146
Criscuoli M, Lippi A, Mengozzi G, Sardelli G, Subissi A, Giachetti A (1993) Pharmacokinetics and pharmacodynamics of idrapril in rats, dogs, and humans. Drug Metab Disp 21:835–840
Zanchi A, Nussberger J, Criscuoli M, Capone P, Brunner HR (1994) Angiotensin converting enzyme inhibition by hydroxamic zinc-binding ligand idrapril in humans. J Cardiovasc Pharmacol 24:317–322
Kronmal RA, Rutan GH, Manolio TA, Borhani NO (1993) Properties of the random zero sphygmomanometer. Hypertension 21:632–637
Cushman DW, Cheung HS (1971) Concentration of angiotensin converting enzyme in tissues of the rat. Biochem Biophys Acta 250:261–265
Menard J, Guyenne T-T, Corvol P, Pau B, Simon D, Roncucci R (1985) Direct immunometric assay of active renin in human plasma. J Hypertens 3 [Suppl 3]:S275-S278
Taddei S, Favilla S, Duranti P, Simonini N, Salvetti A (1991) Vascular renin-angiotensin system and neurotransmission in hypertensive persons. Hypertension 18:266–277
Taddei S, Virdis A, Abdel-Haq B, Giovannetti R, Duranti P, Arena AM, Favilla S, Salvetti A (1993) Indirect evidence for vascular uptake of circulating renin in hypertensive patients. Hypertension 21:852–860
Richer C, Bah M, Cadilhac M, Thuillez C, Giudicelli GF (1986) Cimetidine does not alter free unchanged captopril pharmacokinetics and biological effects in healthy volunteers. J Pharmacol 17:338–342
Olson SC, Horwath AM, Michiniewicz BM, Sedman AJ, Colburn WA, Welling PG (1989) The clinical pharmacokinetics of quinapril. Angiology 40:351–359
Singhvi SM, Duchin KL, Morrison RA, Willard DA, Everett DW, Frantz M (1988) Disposition of fosinopril sodium in healthy subjects. Br J Clin Pharmacol 25:9–15
Vander AJ, Miller R (1964) Control of renin secretion in the anesthetized dog Am J Physiol 297:537–546
De Champlain J, Genest J, Veyrat R (1965) Factors controlling renin in man Trans Assoc Am Physicians 78:135–157
Dzau VJ (1987) Implications of local angiotensin production in cardiovascular physiology and pharmacology. Am J Cardiol 59:59A-65A
Okunishi H, Miyazaki M, Okamura T, Toda N (1987) Different distribution of two types of angiotensin II-generating enzymes in the aortic wall. Biochem Biophys Res Commun 149:1186–1192
Sealey JE, Laragh JH (1990) The renin-angiotensin-aldosterone system for normal regulation of blood pressure and sodium and potassium homeostasis. In: Laragh JH, Brenner BM (eds) Hypertension: pathophysiology, diagnosis, and management. Raven Press, New York 1287–317
Waeber B, Brunner H, Brunner D, Curtet AL, Turini G, Gavras H (1980) Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril. Hypertension 2:236–242
Gohlke P, Linz W, Schölkens B, Kuwer I, Bratenbach S, Schnell A, Unger T (1994) Angiotensin-converting enzyme inhibition improves cardiac function. Role of bradykinin. Hypertension 23:411–418
Erdös EG, Skidgel RA (1987) The angiotensin I-converting enzyme. Lab Invest 56:345–348
Wong PY, Talamo RC, William GH, Colman RW (1975) Response of the kallikrein-kinin and renin-angiotensin systems to saline infusion and upright posture. J Clin Invest 55:691–698
Assad MM, Antonaccio MJ (1982) Vascular wall renin in spontaneously hypertensive rats: Potential relevance to hypertension maintenance and antihypertensive effect of captopril. Hypertension 1982; 4:487–493
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Taddei, S., Ghiadoni, L., Mattei, P. et al. Humoral and haemodynamic effects of idrapril calcium, the prototype of a new class of ACE-inhibitors, in essential hypertensive patients. Eur J Clin Pharmacol 48, 339–343 (1995). https://doi.org/10.1007/BF00194948
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00194948