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

Aims

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.

Methods

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.

Results

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).

Conclusions

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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