Effect of Severe Renal Failure and Haemodialysis on the Pharmacokinetics of Levosimendan and Its Metabolites - Clinical Pharmacokinetics

Effect of Severe Renal Failure and Haemodialysis on the Pharmacokinetics of Levosimendan and Its Metabolites - Clinical Pharmacokinetics

Jaakko Puttonen;Sampo Kantete;Matti Kivikko;Sari Häkkinen;Veli-Pekka Harjola;Petri Koskinen;Pertti J. Pentikäinen;Jaakko Puttonen;Sampo Kantete;Matti Kivikko;Sari Häkkinen;Veli-Pekka Harjola;Petri Koskinen;Pertti J. Pentikäinen;
clinical pharmacokinetics 2012 Vol. 46 pp. 235-246
247
puttonen2012clinicaleffect

Abstract

Background and objectives Levosimendan is a calcium sensitiser developed for the treatment of congestive heart failure. It increases myocardial contractility, reduces the filling pressure and dilates both the peripheral and coronary vessels. The circulating metabolites of levosimendan, OR-1855 and OR-1896, are formed and eliminated slowly after intravenous administration of levosimendan. The aim of this study was to investigate the effect of impaired renal function and haemodialysis on the pharmacokinetics of levosimendan, OR-1855 and OR-1896. Study design This study was an open-label, nonrandomised, phase I pharmacokinetic study. Levosimendan was administered as a single-dose infusion of 0.1 μg/kg/minute for 24 hours. The follow-up period lasted 3 weeks. Study setting Twenty-five patients were included: 12 patients with severe chronic renal failure (CRF) with creatinine clearance of

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