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

AbstractAIMS:
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 micro g kg(-1) min(-1) and 12 at a rate 0.1 micro g 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.
AuthorsSaila Antila, Matti Kivikko, Lasse Lehtonen, Jaan Eha, Aira Heikkilä, Pasi Pohjanjousi, Pertti J Pentikäinen
JournalBritish journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 57 Issue 4 Pg. 412-5 (Apr 2004) ISSN: 0306-5251 [Print] England
PMID15025738 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Controlled Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Acetamides
  • Cardiotonic Agents
  • Hydrazones
  • N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide
  • Pyridazines
  • Simendan
Topics
  • Acetamides (metabolism)
  • Cardiotonic Agents (administration & dosage, pharmacokinetics)
  • Female
  • Heart Failure (drug therapy, metabolism)
  • Humans
  • Hydrazones (administration & dosage, metabolism, pharmacokinetics)
  • Infusions, Intravenous
  • Male
  • Protein Binding
  • Pyridazines (administration & dosage, metabolism, pharmacokinetics)
  • Simendan

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