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

  1. Saila Antila1,*,
  2. Matti Kivikko1,
  3. Lasse Lehtonen1,†,
  4. Jaan Eha2,
  5. Aira Heikkilä1,
  6. Pasi Pohjanjousi1,
  7. Pertti J. Pentikäinen3

Article first published online: 3 FEB 2004

DOI: 10.1111/j.1365-2125.2003.02043.x

Issue

British Journal of Clinical Pharmacology

British Journal of Clinical Pharmacology

Volume 57, Issue 4, pages 412–415, April 2004

Additional Information

How to Cite

Antila, S., Kivikko, M., Lehtonen, L., Eha, J., Heikkilä, A., Pohjanjousi, P. and Pentikäinen, P. J. (2004), Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan. British Journal of Clinical Pharmacology, 57: 412–415. doi: 10.1111/j.1365-2125.2003.02043.x

Author Information

  1. 1

    Orion Pharma, Research Centre, Espoo, Finland,

  2. 2

    Mustamae Hospital, Tallinn, Estonia and

  3. 3

    Helsinki University Central Hospital, Department of Internal Medicine, Helsinki, Finland

  1. †

    Present address: Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland

*Saila Antila, Orion Pharma, Research Center, P.O. Box 65, FIN-02101 Espoo, Finland. Tel: + 358 10 429 2152 Fax: + 358 10 429 2896 E-mail: saila.antila@luukku.com

Publication History

  1. Issue published online: 3 FEB 2004
  2. Article first published online: 3 FEB 2004
  3. Received14 May 2002 Accepted29 October 2003

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Keywords:

  • levosimendan;
  • pharmacokinetics;
  • metabolism;
  • calcium sensitizer

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.

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