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

Article date: April 2004

By: Saila Antila, Matti Kivikko, Lasse Lehtonen, Jaan Eha, Aira Heikkilä, Pasi Pohjanjousi, Pertti J. Pentikäinen, in Volume 57, Issue 4, pages 412-415


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 µg kg−1 min−1 and 12 at a rate 0.1 µg 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.

DOI: 10.1111/j.1365-2125.2003.02043.x

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