Pharmacodynamics and pharmacokinetics of oral Levosimendan and its metabolites in patients with severe congestive heart failure:: A dosing interval study

The objective of this study was to explore the pharmacodynamics and pharmacokinetics of oral levosimendan in patients with severe congestive heart failure. This was a randomized.. parallel-group, double-blind, placebo-con trolled trial. Oral levosimendan 2 to 8 mg daily or placebo was administered to 25 patients with New York Heart Association class III-IV congestive heart failure for 4 weeks. Pharmacodynamic variables consisted of heart rate-corrected electromechanical systole, heart rate, and systolic and diastolic blood pressure. The pharmocokinetics of levosimendan and its metabolites.. OR-1855 and OR-1896, was assessed. The 4- to 8-mg daily doses of oral levosimendan showed moderate inotropic effects. Blood pressure remained unchanged with all doses. A moderate increase in heart rate was observed except with the 2-mg dose, Pharmacokinetic parameters of the metabolites increased linearly with the dose (Pless than or equal to.002 for C-max and AUG(0-8h) for both treatment groups). It was concluded that oral levosimendan has inotropic and chronotropic effects in patients with severe congestive heart failure. Plasma concentrations of its metabolites increase dose dependently.