Pharmacokinetic and Pharmacodynamic Properties of Ramipril in Patients with Congestive Heart Failure (NYHA III-IV)

Gerckens, Ulrich; Grube, E; Mengden, T; Sigel, H; Wagner, Willi L.; Lahn, T.; Irmisch, R; Metzger, H.

doi:10.1097/00005344-198900133-00012

Cited by 16 publications

(11 citation statements)

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“…The pharmacokinetics of ramipril after singledose administration of the drug have been investigated in patients with cardiac failure (New York Heart Association grades III to IV) in a noncomparative trial, with a lO-day follow-up period (Gerckens et al 1989). The Cmax of ramipril was 57 ± 26.8 Jlg/L and occurred 1.4 hours after administration of ramipril 5mg; the elimination t'i2 was 13 2.4 ± 1.2 hours.…”

Section: Patients With Congestive Heart Failurementioning

confidence: 99%

Clinical Pharmacokinetics of Ramipril

Meisel

Shamiss

Rosenthal

1994

Clinical Pharmacokinetics

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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.

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Section: Patients With Congestive Heart Failurementioning

confidence: 99%

Clinical Pharmacokinetics of Ramipril

Meisel

Shamiss

Rosenthal

1994

Clinical Pharmacokinetics

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“…Ramipril is a potent and long-acting angiotensin-converting enzyme (ACE) inhibitor [1][2][3] that is used for treatment of essential hypertension [4][5][6][7] and congestive heart failure [8,9]. Clinical trials in patients with mild to moderate hypertension demonstrated that treatment with a single daily dose of 2.5-5 mg ramipril was effective in two-thirds of hypertensive patients [2,10,11].…”

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confidence: 99%

Pharmacokinetics, pharmacodynamics and bioavailability of the ACE inhibitor ramipril

Griensven

Schoemaker

Cohen

et al. 1995

Eur J Clin Pharmacol

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The pharmacokinetics and pharmacodynamics of the prodrug ramipril and its active ACE-inhibiting metabolite ramiprilat were investigated in an open, randomised, three-way cross-over study in 12 healthy male volunteers. Subjects received 2.5 mg ramipril orally, 2.5 mg ramipril intravenously and 2.5 mg ramiprilat intravenously. The absolute bioavailability as judged by ramipril plasma AUC was 15%, by ramiprilat plasma AUC, 44%. Ramiprilat formation from intravenous ramipril was 53% and from oral ramipril 28%. Urinary recovery of oral ramipril was 23%, i.v. ramipril 49%, and i.v. ramiprilat 68% of the given dose. Maximum ACE inhibition was highest (100%) after i.v. ramiprilat; it was 99% after i.v. ramipril and 84% following oral ramipril. ACE inhibition over 24 h was highest after i.v. ramipril, 2% less with i.v. ramiprilat and 34% less with oral ramipril. Ramiprilat renal clearance was concentration dependent. The biological availability of ramipril can best be judged by ramiprilat AUC, urinary recovery of ramipril and metabolites, or ACE inhibition over 24 h. It is concluded that the bioavailability of oral ramipril seems to be in the range of 44-66%.

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“…Gautam et al [9] reported similar findings and proposed that lisinopril dosage should be adjusted on the basis of renal function in elderly patients with CHF. Differences in ramipril pharmacokinetics between patients with CHF and normal subjects may also be attributable to reduced renal function in elderly patients with CHF [10].…”

Section: Discussionmentioning

confidence: 99%

“…Twelve outpatients (10 Physical examination was performed at screening and again 24 h after the last dose of quinapril. Recumbent blood pressures and heart rates were measured at screening and again at the end of the study.…”

Section: Subjectsmentioning

confidence: 99%

The pharmacokinetics of quinapril and quinaprilat in patients with congestive heart failure.

Begg

Robson

Ikram

et al. 1994

Brit J Clinical Pharma

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The pharmacokinetics of quinapril and its active metabolite quinaprilat were studied in 12 patients with congestive heart failure (CHF) after multiple oral doses of 10 mg quinapril twice daily. Six patients had an ejection fraction of <35% and six had an ejection fraction between 35%-50%. Increases in the apparent elimination half-life and in AUC(O, 1 2h) values of quinaprilat were associated with smaller ejection fractions, decreased creatinine clearance, and increased patient age. Comparison with data from age-matched controls having comparable renal function suggests that creatinine clearance is the major determinant of quinaprilat clearance. CHF per se appears to have minimal effect. Dosing of quinapril in patients with CHF should be based on their renal function.

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Pharmacokinetic and Pharmacodynamic Properties of Ramipril in Patients with Congestive Heart Failure (NYHA III-IV)

Cited by 16 publications

References 0 publications

Clinical Pharmacokinetics of Ramipril

Clinical Pharmacokinetics of Ramipril

Pharmacokinetics, pharmacodynamics and bioavailability of the ACE inhibitor ramipril

The pharmacokinetics of quinapril and quinaprilat in patients with congestive heart failure.

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