Summary
The aim of the present study was primarily to evaluate the haemodynamic effects of the ACE-inhibitor ramipril which is active via its metabolite ramiprilat. Ramipril 1.25, 2.5 and 5 mg and placebo was administered orally to 4 groups of 12 patients with heart failure (NYHA III) in a double-blind randomised, parallel study. Haemodynamics were monitored for 24 h and blood was sampled and urine collected for up to 96 h.
In the placebo-treated group the cardiac index (CI) was significantly increased (15.8%) and right atrial pressure decreased (26.6%). Ramipril 1.25 mg had insignificant haemodynamic effects compared to placebo and the 2.5 mg dose had significant effects on some haemodynamic variables. Ramipril 5 mg had pronounced and sustained effects on pulmonary artery pressure, which fell by 43.7%, and pulmonary capillary wedge pressure (PCWP; −59.1%); systemic vascular resistance was also decreased 21%. A significant effect on CI was only seen after 2.5 mg ramipril (+7.4%). The mean maximal degree of ACE inhibition was 73.2, 90.4 and 98.5%, respectively, after the three doses of ramipril. Complete inhibition of ACE-activity was seen at a mean plasma concentration of ramiprilat of 4.7 ng·ml−1. The degree of inhibition declined with a half life of about 75 h.
There was a significant relation between the degree of ACE-inhibition and change in PCWP but not with the change in SVR. Ramipril was mainly eliminated in the form of ramiprilat and inactive metabolites.
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References
Witte PU, Irmisch R, Hajdù P, Metzger H (1984) Pharmacokinetics and pharmacodynamics of a novel orally active angiotensin converting enzyme inhibitor (HOE 498) in healthy subjects. Eur J Clin Pharmacol 27: 577–581
Crozier IG, Ikram H, Nicholls MG, Jans S (1989) Global and regional hemodynamic effects of ramipril in congestive heart failure. J Cardiovasc Pharmacol. 14: 688–693
de Graeff PA, Kingma JH, Viersma JW, Wesseling H, Lie KI (1989) Acute and chronic effects of ramipril and captopril in congestive heart failure. Int J Cardiol 23: 59–67
Vogt A, Unterberg C, Kreuzer H (1987) Acute effects of the new angiotensin converting enzyme inhibitor ramipril on hemodynamics and carotid sinus baroretlex activity in congestive heart failure. Am J Cardiol 59: 149D-154D
Herrlin B, Sylvén C, Nyquist O, Edhag O (1990) Short-term haemodynamic effects of converting-enzyme inhibition before and after eating in patients with moderate heart failure caused by dilated cardiomyopathy: a double-blind study. Br Heart J 63: 26–31
Eckert HG, Münscher G, Oekonomopulos R, Strecker H, Urbach H, Wissmann (1985) A radioimmunoassay for the angiotensin converting enzyme inhibitor ramipril and its active metabolite. Arzneimittelforschung/Drug Res 35: 1251–1256
Hajdú P, Schmidt D, Bomm M, Hack L, Keller A (1984) Determination of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) and its hydrolysis product in serum and urine. Arzneimittelforschung/Drug Res 34: 1431–1435
Metzger H, Maier R, Sitter C, Stern H-O (1984) 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S, 3S, 5S)-2-azabicyclo [3.3.0]octane-3-carboxylic acid (Hoe 498) — a new and highly effective angiotensin I converting enzyme inhibitor. Arzneimittelforschung/Drug Res. 34: 1402–1406
Malvano R, Zuchelli GC, Rosa U, Salvetti A (1972) Measurement of plasma renin activity by angiotensin I radioimmunoassay. I. An assessment of some methodological aspects. J Nucl Biol Med 16: 24–31
Ferreira SR, Saragoça MA, Homsi E, Ajzen H, Draibe SA, Ribeiro AB, Ramos OL (1987) Acute hemodynamic action of captopril in congestive heart failure: contrasts between refractory and untreated patients. J Clin Hypertens 3: 685–694
Mulligan IP, Fraser AG, Tirlapur V, Lewis MJ, Newcombe RG, Henderson AH (1988) A randomised cross-over study of enalapril in congestive heart failure: haemodynamic and hormonal effects during rest and exercise. Eur J Clin Pharmacol 34: 323–331
Cushman DW, Wang FL, Fung WC, Grover GJ, Harvey CM, Scalese RJ, Mitch SL, Deforrest JM (1989) Comparisons in vitro, ex vivo, and in vivo of the actions of seven structurally diverse inhibitors of angiotensin converting enzyme (ACE) Br J Clin Pharmacol 28: 115S-131S
Kaplan HR, Taylor DG, Olson SC, Andrews LK (1989) Quinapril — a preclinical review of the pharmacology, pharmacokinetics, and toxicology. Angiology 140: 335–350
Flapan AD, Shaw TRD, Edwards CRW, Rademaker M, Davies E, Williams BC (1992) Lack of correlation between the acute haemodynamic response to intravenous captopril and plasma concentrations of angiotensin II in patients with chronic cardiac failure. Eur J Clin Pharmacol 43: 1–5
Aurell M, Delin K, Herlitz H, Ljungman S, Witte PU et al (1987) Pharmacokinetics and pharmacodynamics of ramipril in renal failure. Am J Cardiol 59: 65D-69D
Debusmann ER, Pujadas JO, Lahn W, Irmisch R, Jané F etal (1987) Influence of renal function on the pharmacokinetics of ramipril (HOE 498). Am J Cardiol 59: 70D-78D
Manthey J, Osterziel J, Röhrig N, Dietz R, Hackenthal E etal (1987) Ramipril and captopril in patients with heart failure: effects on hemodynamics and vasoconstrictor systems. Am J Cardiol 59: 171D-175D
de Leeuw PW, Lugtenburg PL, van Houten H, Looman JHM, Birkenhäger WH (1985) Preliminary experiences with HOE 498, a novel long-acting converting enzyme inhibitor, in hypertensive patients. J Cardiovasc Pharmacol 7: 1161–1165
Ball SG, Robertson JIS (1987) Clinical pharmacology of ramipril. Am J Cardiol 59: 23D-27D
Gerckens U, Grube E. Mengden T, Sigel H, Wagner W-L et al (1987) Pharmacokinetic and pharmacodynamic properties of ramipril in patients with congestive heart failure (NYHA III-IV). J Cardiovasc Pharmacol 13 [Suppl 3]: 49–51
Meyer BH, Müller FO, Badian M, Eckert HG, Hajdù P et al (1987) Pharmacokinetics of ramipril in the elderly. Am J Cardiol 59: 33D-37D
Eckert HG, Badian MJ, Gantz D, Kellner HM, Volz M (1984) Pharmacokinetics and biotransformation of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyclo [3.3.0] octane-3-carboxylic acid (Hoe 498) in rat, dog and man. Arzneimittelforschung 34: 1435–1447
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Beermann, B., Nyquist, O., Höglund, C. et al. Acute haemodynamic effects and pharmacokinetics of ramipril in patients with heart failure. Eur J Clin Pharmacol 45, 241–246 (1993). https://doi.org/10.1007/BF00315390
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DOI: https://doi.org/10.1007/BF00315390