Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan

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Abstract
The purpose of the study was to characterize the pharmacokinetics of levosimendan and its metabolites OR-1855 and OR-1896 in patients with congestive heart failure. Levosimendan was administered as a continuous intravenous infusion for 7 days. Twelve subjects received the drug at an infusion rate of 0.05 micro g kg(-1) min(-1) and 12 at a rate 0.1 micro g kg(-1) min(-1). Steady state concentrations of levosimendan were achieved within 4 h. Peak concentrations of the metabolites occurred after termination of the infusion. The mean (+/- SD) half-life of the active metabolite OR-1896 was 81 +/- 37 h after the lower dose and 81 +/- 28 h after the higher dose (P = 0.992, 95% confidence interval on the difference -27.5, 27.7). The metabolites of levosimendan, OR-1855 and OR-1896, were formed and eliminated slowly, their peak concentrations occurring after termination of the 7-day infusion of the drug.