Authors: Antila S.¹; Kivikko M.¹; Lehtonen L.; Eha J.²; Heikkilä A.¹; Pohjanjousi P.¹; Pentikäinen P.J.³

Source: British Journal of Clinical Pharmacology, Volume 57, Number 4, April 2004 , pp. 412-415(4)

Publisher: Wiley-Blackwell

Abstract:

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.

Keywords: levosimendan; pharmacokinetics; metabolism; calcium sensitizer

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2125.2003.02043.x

Affiliations: 1: Orion Pharma, Research Centre, Espoo, Finland, 2: Mustamae Hospital, Tallinn, Estonia and 3: Helsinki University Central Hospital, Department of Internal Medicine, Helsinki, Finland

Publication date: 2004-04-01

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