A Pharmacokinetic and Pharmacodynamic Study of Intravenous Levosimendan in Healthy Chinese Volunteers and Ethnic Comparisons.

BACKGROUND The objective of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous levosimendan and the metabolites (OR1855 and OR1896) in healthy Chinese male subjects and to post hoc compare with Caucasian subjects. METHODS One single 2 mg dose of levosimendan was infused intravenously over 10 minutes to each of 14 healthy male subjects. Plasma levosimendan was analyzed by high performance liquid chromatography. Pharmacodynamics was evaluated using echocardiography. RESULTS The Cmax (peak concentration) and AUC∞ (area under the curve from time 0 to infinity) of levosimendan of Chinese subjects were significantly higher than for Caucasian subjects as 256.1 ± 37.8 (mean ± SD) vs. 142.1 ± 17.5 ng/mL and 207.5 ± 35.2 vs. 117.0 ± 17.0 hr·ng/mL, respectively. The clearance of Chinese subjects was significantly lower than Caucasian subjects at 9.9 ± 1.8 vs. 17.4 ± 2.7 L/hr, respectively. The elimination half-life of Chinese subjects was significantly longer than for Caucasian subjects (1.18 ± 0.18 vs. 0.76 ± 0.10 hr, respectively). Chinese subjects eliminated levosimendan significantly slower than Caucasian subjects, leading to a higher exposure of levosimendan in Chinese subjects. However, this higher exposure did not significantly change the most pharmacodynamic properties of levosimendan except for ejection fraction (EF). The EF increased 12.2 ± 11.4% in Chinese subjects 20 min after the end of intravenous infusion, which was significantly lower than Caucasian subjects with EF increased by 22.7 ± 7.0%. CONCLUSIONS The intravenous levosimendan in healthy Chinese volunteers was safe, and well-tolerated with significant inotropic effect. The clearance of levosimendan of Chinese subjects was significantly lower and elimination half-life longer than Caucasian subjects. KEY WORDS Chinese; Ethnic comparison; Levosimendan; Pharmacodynamics; Pharmacokinetics; Volunteer.