title: Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan.
abstract: OBJECTIVE
  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.
authors.affiliation: Orion Pharma, Research Centre, Espoo, Finland. saila.antila@luukku.com
authors.forename: Saila
authors.initials: S
authors.lastname: Antila
authors.forename: Matti
authors.initials: M
authors.lastname: Kivikko
authors.forename: Lasse
authors.initials: L
authors.lastname: Lehtonen
authors.forename: Jaan
authors.initials: J
authors.lastname: Eha
authors.forename: Aira
authors.initials: A
authors.lastname: Heikkilä
authors.forename: Pasi
authors.initials: P
authors.lastname: Pohjanjousi
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Pentikäinen
mesh_terms: D000081:Acetamides / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D011485:Protein Binding; D011724:Pyridazines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D000077464:Simendan
chemical_list: D000081:Acetamides; D002316:Cardiotonic Agents; D006835:Hydrazones; C414222:N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide; D011724:Pyridazines; D000077464:Simendan