Summary
Ramipril is a long-acting nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor introduced for clinical use about a decade ago. Ramipril is a prodrug that undergoes de-esterification in the liver to form ramiprilat, its active metabolite. Ramipril rapidly distributes to all tissues, with the liver, kidneys and lungs showing markedly higher concentrations of the drug than the blood. After absorption from the gastrointestinal tract, rapid hydrolysis of ramipril occurs in the liver. In the therapeutic concentration range, protein binding of ramipril and ramiprilat is 73 and 56%, respectively. Ramiprilat binds to ACE with high affinity at concentrations similar to that of the enzyme and establishes equilibrium slowly.
Although ramipril is metabolised by hepatic and renal mechanisms to both a glucuronate conjugate and a diketopiperazine derivative, most of the drug is excreted in the urine as ramiprilat and the glucuronate conjugate of ramiprilat. Elimination from the body is characterised by a relatively rapid initial phase with a half-life of 7 hours and a late phase with a half-life of about 120 hours.
No clinically significant pharmacokinetic interactions between ramipril and other drugs have been reported. The drug has been generally well tolerated with the most prevalent adverse effects being dizziness (3.4%), headache (3.2%), weakness (1.9%) and nausea (1.7%).
Ramipril is an effective and well tolerated drug for the treatment of hypertension and congestive heart failure in all patients, including those with renal or hepatic dysfunction, and the elderly.
Similar content being viewed by others
References
Aurell M, Delin K, Herlitz H, Ljungman S, Witte PU, et al. Pharmacokinetics and pharmacodynamics of ramipril in renal failure. American Journal of Cardiology 59: 65D–69D, 1987
Bainbridge AD, MacFadyen RJ, Lees KR, Reid JL. A study of the acute pharmacodynamic interaction of ramipril and felodipine in normotensive subjects. British Journal of Clinical Pharmacology 31(2): 148–153, 1991
Ball SG, Robertson JIS. Clinical pharmacology of ramipril. American Journal of Cardiology 59: 65D–69D, 1987
Bauer B, Lorenz H, Zahlten R. An open multicenter study to assess the long term efficacy, tolerance, and safety of the angiotensin converting enzyme inhibitor ramipril in patients with mild to moderate essential hypertension. Journal of Cardiovascular Pharmacology 13 (Suppl. 3): S70–S74, 1989
Bender N, Rangoonwala B, Rosenthal J, Vasmant D. Physicochemical and enzyme binding kinetic properties of a new angiotensin-converting enzyme inhibitor, ramipril, and their clinical implications. Clinical Physiology and Biochemistry 8 (Suppl. 1): 44–52, 1990
Boeijinga JK, Matroos AW, Van Maarschalkerweed MW, Jertich-Bastiaanse A, Breimer DD. No interaction shown between ramipril and coumarin derivatives. Current Therapeutic Research 44: 902–908, 1988
Brogden RN, Todd PA, Sorkin EM. Captopril: an update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension and congestive heart failure. Drugs 36: 540–600, 1988
Bünning P. Inhibition of angiotensin converting enzyme by 2-[N-[(S)-1-carboxy-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyclo (3.3.0) octane-3-carboxylic acid (HOE 498 Diacid): comparison with captopril and enalaprilat. Arzneimittel-Forschung (Drug Research) 34(II): 1406–1410, 1984
Debusmann ER, Pujadas JO, Lahn W, Irmisch R, Jane F, et al. Influence of renal function on the pharmacokinetics of ramipril (HOE 498). American Journal of Cardiology 59: 70D–78D, 1987
De Leeuw PW, Ammerdorfer TH, Birkenhager WH. Experience with HOE 498, a long-acting converting enzyme inhibitor. Second European Meeting on Hypertension, Milan, June 9–12. Abstract no. 130, 1985
Doering W, Maass L, Irmisch R, Konig E. Pharmacokinetic interaction study with ramipril and digoxin in healthy volunteers. American Journal of Cardiology 59: 60D–64D, 1987
Eckert HG, Badian MJ, Gantz D, Kellner HM, Volz M. Pharmacokinetics and biotransformation of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl] — L-alanyl]-(1S,3S,5S)-azabicyclo[3.3.0]octane-3-carboxylic acid (HOE 498) in rat, dog and man. Arzneimittel-Forschung 34: 1435–1477, 1984
Eckert HG, Munscher G, Oekonomopulos R, Strecker H, Urbach H, et al. A radioimmunoassay for the angiotensin converting enzyme inhibitor ramipril and its active metabolite. Arzneimittel-Forschung 35: 1251–1256, 1985
Gerckens U, Grube E, Mengden T, Sigel H, Wagner WL, et al. Pharmacokinetic and pharmacodynamic properties of ramipril in patients with congestive heart failure (NYHA III-IV). Journal of Cardiovascular Pharmacology 13 (Suppl. 3): 549–551, 1989
Gilchrist WJ, Beard K, Manhem P, Thomas EM, Robertson JIS, et al. Pharmacokinetics and effects on the renin-angiotensin system of ramipril in elderly patients. American Journal of Cardiology 59: 28D–32D, 1987
Hajdu P, Bomm M, Hack L, Keller A. Detemunation of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-azabicyclo[3.3.0] octane-3-carboxylic acid (HOE 498) and its hydrolysis product in serum and urine. Arzneimittel-Forschung (Drug Research) 34(II): 1431–1439, 1984
Harada A, Inenaga T, Washio M. Pharmacokinetics of ramipril in chronic renal failure. Current Therapeutic Research 44: 200–212, 1988
Hosie J, Meredith P. The pharmacokinetics of ramipril in a group of ten elderly patients with essential hypertension. Journal of Cardiovascular Pharmacology 18 (Suppl. 2): S125–S127, 1991
Kaneko Y, Omae T, Yoshinaga K, Iimura O, Inagaki Y, et al. Effect of ramipril, a new angiotensin converting enzyme inhibitor, on diurnal variations of blood pressure in essential hypertension. American Journal of Cardiology 59: 86D–91D, 1987
Kondo K, Ohashi K, Saruta T, Shimura M, Yotodera K. Tolerability, pharmacodynamics and pharmacokinetics of HOE 498 after multiple administration of 5 mg for 15 days in healthy male subjects. Japanese Pharmacology and Therapeutics 14: 339–359, 1986
Manhem PJO, Ball SG, Morton JJ, Murray GD, Leckie BJ, et al. A dose response study of HOE 498, a new non-sulfhydril converting enzyme inhibitor, on blood pressure, pulse rate and the renin-angiotensin aldosterone system in normal man. British Journal of Clinical Pharmacology 20: 27–35, 1985
Meisel S, Shamiss A, Verho MT, Rosenthal T. Ramipril in the treatment of severe hypertension: pharmacokinetics and clinical efficacy. Current Therapeutic Research 49(6): 1–6, 1991
Metzger H, Maier L, Sitter C, Stern HO. 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. Arzneimittel-Forschung 34(11): 1402–2405, 1984
Meyer BH, Muller FO, Badian M, Eckert HG, Hajdu P, et al. Pharmacokinetics of ramipril in the elderly. American Journal of Cardiology 59: 33D–37D, 1987
Schunkert H, Kindler J, Gassman M, Lahn W, Irmisch R, et al. Pharmacokinetics of ramipril in hypertensive patients with renal insufficiency. European Journal of Pharmacology 37: 249–256, 1989
Shapiro R. Activation and inactivation of rabbit pulmonary angiotensin converting enzyme, PhD Thesis, Harvard University, Cambridge, 1983
Shionoiri H, Ikeda Y, Kimura K, Miyakawa T, Kaneko Y. Pharmacodynamics and pharmacokinetics of single-dose ramipril in hypertensive patients with various degrees of renal function. Current Therapeutic Research 40: 74–85, 1986
Shionoiri H, Miyakawa T, Yasuda G, Ishikawa Y, Umemura S, et al. Pharmacokinetics of a single dose of ramipril in patients with renal dysfunction: comparison with essential hypertension. Journal of Cardiovascular Pharmacology 10 (Suppl. 7): S145–S147, 1987
Todd PA, Benfield P. Ramipril: a review of its pharmacological properties and therapeutic efficacy in cardiovascular disorders. Drugs 39: 110–135, 1990
Todd PA, Heel RC. Enalapril: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension and congestive heart failure. Drugs 31: 198–248, 1986
Vasmant D, Bender N. The renin-angiotensin system and ramipril, a new converting enzyme inhibitor. Journal of Cardiovascular Pharmacology 14 (Suppl. 4): S46–S52, 1989
Verho M, Malerczyk V, Grotsch H, Zenbil I. Absence of interaction between ramipril, a new ACE-inhibitor, and phenprocoumon, an anticoagulant agent. Pharmatherapeutica 5: 392–399, 1989
Witte PU, Irmisch R, Hajdu P, Metzger H. Pharmacokinetics and pharmacodynamics of a novel orally active angiotensin converting enzyme inhibitor (HOE 498) in healthy subjects. European Journal of Clinical Pharmacology 27: 577–581, 1984
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Meisel, S., Shamiss, A. & Rosenthal, T. Clinical Pharmacokinetics of Ramipril. Clin. Pharmacokinet. 26, 7–15 (1994). https://doi.org/10.2165/00003088-199426010-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-199426010-00002