Summary
The pharmacological activity and safety of the new angiotensin converting enzyme (ACE) inhibitor trandolapril (RU 44570) has been evaluated in ten healthy male volunteers given 2 mg once daily for seven days. Assessment criteria included evaluation of plasma ACE and renin activity and aldosterone levels in the supine and standing positions, monitoring of blood pressure, heart rate and electrocardiogram, routine blood and urine laboratory tests, and evaluation of adverse effects.
Plasma ACE activity (both in the supine and standing positions) was significantly lower after the first dose and was almost completely suppressed after 7 days of treatment. Plasma renin activity with the subjects in both positions was significantly increased at the end of treatment. Plasma aldosterone did not vary significantly, except for an increase in the standing position after 7 days of washout. No significant changes occurred in blood pressure, heart rate, electrocardiogram, blood or urine laboratory tests. No adverse effects were reported, in particular, no orthostatic hypotension, cough or episodes of bronchospasm occurred.
It is concluded that oral trandolapril 2 mg o.d. is an effective and long-lasting ACE inhibitor with a good safety profile on repeated dosing. Further studies are warranted to investigate its therapeutic application as well as its safety profile after long-term administration.
Similar content being viewed by others
References
Atlas SA, Niarchos AP, Case DB (1983) Inhibitors of the renin-angiotensin system. Effects on blood pressure, aldosterone secretion and renal function. Am J Nephrol 3: 118–127
Brogden RN, Todd PA, Sorkin EM (1988) Captopril. An update of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs 36: 540–600
Brown NL, Badel MY, Benzoni F, Zaniroto J, Vincent JC, Fichelle J, Worcel M (1988) Angiotensin converting enzyme inhibition, antihypertensive activity and haemodynamic profile of trandolapril (RU 44570). Eur J Pharmacol 148: 79–91
Brown NL, Chevillard C, Worcel M (1987a) Differences between trandolapril and enalapril for inhibition of tissue ACE activity in rats. Br J Pharmacol 90: 204
Brown NL, Fichelle J, Vincent JC, Worcel M (1987b) Cardiovascular profile of trandolapril, a new angiotensin converting enzyme inhibitor. Br J Pharmacol 90: 203
Chevillard C, Jouguey S, Mathieu MN, Brown NL, Laliberte' F, Hamon G (1989) Compared effects of trandolapril (RU 44570) and enalapril on blood pressure, cardiac hypertrophy and tissue angiotensin converting enzyme activity in SH rats. Fundam Clin Pharmacol 3: 131
Douglas WW (1985) Polypeptides-Angiotensin, plasma kinins and others. In: Goodman Gilman A, Goodman LS, Rall TW, Murad F (eds) The Pharmacological Basis of Therapeutics. MacMillan, New York, pp 639–659
Dzau VJ (1988) Tissue renin-angiotensin system: physiologic and pharmacologic implications. Circulation 77 [Suppl 1]: I1-I3
Frohlich ED (1989) Angiotensin-converting enzyme inhibitors-Present and future. Hypertension 13 [Suppl 1]: I125-I130
Gavras H (1988) The place of angiotensin-converting enzyme inhibition in the treatment of cardiovascular disease. N Engl J Med 319: 1541–1543
Gavras H, Gavras I (1988) Angiotensin converting enzyme inhibitors. Properties and side effects. Hypertension 11 [Suppl II]: 37–41
Gordon H, Williams MD (1988) Converting enzyme inhibitors in the treatment of hypertension. N Engl J Med 319: 1517–1525
Lijnen P, Staessen J, Fagard R, Amery A (1982) Increase in plasma aldosterone during prolonged captopril treatment. Am J Cardiol 49: 1561–1563
Macfadyen RJ, Lees KR, Reid JL (1990) Perindopril: a review of its pharmacokinetics and clinical pharmacology. Drugs 39 [Suppl 1]: 49–63
Manhem PJO, Ball SG, Morton JJ, Murray GD, Leckie BJ, Fraser R, Robertson JIS (1985) A dose-response study of HOE 498, a new non-sulphydryl converting enzyme inhibitor, on blood pressure, pulse rate and the renin-angiotensin-aldosterone system in normal man. Br J Clin Pharmacol 20: 27–35
Patat A, Surjus A, Le Go A, Granier J (1989) Safety and tolerance of a single oral dose of trandolapril (RU 44570), a new angiotensin-converting enzyme inhibitor. Eur J Clin Pharmacol 36: 17–23
The Consensus Trial Study Group (1987) Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med 316: 1429–1435
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
De Ponti, F., Marelli, C., D'Angelo, L. et al. Pharmacological activity and safety of trandolapril (RU 44570) in healthy volunteers. Eur J Clin Pharmacol 40, 149–153 (1991). https://doi.org/10.1007/BF00280069
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00280069