Abstract: Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1 was administered at a single dose of 6 μg·kg^-1 levosimendan by intravenous bolus injection within 10 min, and then followed by intravenous infusion for 4 h at a dose per minute of 0.05 μg·kg^-1·min^-1. Similarly, each subject in the group 2(or group 3) was given by intravenous bolus injection at a dose of 12 μg·kg^-1 (or 18 μg·kg^-1) followed by an infusion at a dose of 0.10 μg·kg^-1·min^-1 (or 0.15 μg·kg^-1·min^-1) levosimendan. Blood samples were collected at 0 (prior to dosing), 0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8 and 10 h after administrations. Levosimendan concentrations in plasma were measured by LC-MS/MS method. The pharmacokinetic parameters were calculated using a software Drug and Statistic(version 2.0). Results After administrations of levosimendan at various dose levels, the half-life(t_1/2) values were 1.50 ± 0.35, 1.64 ± 0.25 and 1.54 ± 0.39 h; the maximal concentrations after injections (C₀) were 9.54 ± 3.90, 15.95 ± 7.84 and 28.46 ± 10.74 ng·mL^-1; the areas under concentration-time(AUC_0-t (t = 7, 8)) were 33.63 ± 9.34,54.39 ± 15.34 and 78.36 ± 23.74 ng·mL^-1·h, respectively. Conclusion The C₀ and AUC_0-t values of levosimendan exhibited a dose-dependent manner, respectively. No differences in the pharmacokinetic parameters were observed between male and female Chinese subjects.

Key words: LC-MS/MS, LC-MS/MS, Levosimendan, Levosimendan, Pharmacokinetics, Pharmacokinetics