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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Steady-state kinetics of ramipril in renal failure.

In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 23 hypertensive patients with various degrees of renal insufficiency. During a 2-week treatment period, each subject took daily a 5-mg tablet of ramipril. Serum profiles and urinary excretion of the parent compound and ramiprilat, the active metabolite, were then evaluated. Peak concentrations of ramipril were slightly greater in patients with severe renal insufficiency; however, most of the ramipril was metabolized in the liver. The drug concentration-time curve was almost independent of renal function and no accumulation was observed after multiple dosing. In contrast, ramiprilat kinetics were significantly influenced by renal function. Initial apparent half-lives (8-16 h), mean trough concentrations (5-19 ng/ml), and absolute accumulation all increased with worsening renal function, and renal clearance of ramiprilat was significantly correlated with creatinine clearance. The subsequent long terminal phase at low ramiprilat serum concentration represents the slow dissociation of the angiotensin converting enzyme (ACE)-bound drug. This study indicates that in patients with severe renal insufficiency (creatinine clearance below 30 ml/min), smaller doses of ramipril will be required than in patients with normal or borderline normal renal function.[1]


  1. Steady-state kinetics of ramipril in renal failure. Schunkert, H., Kindler, J., Gassmann, M., Lahn, W., Irmisch, R., Debusmann, E.R., Ocón-Pujadas, J., Sieberth, H.G. J. Cardiovasc. Pharmacol. (1989) [Pubmed]
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