A pharmacokinetic and pharmacodynamic study of intravenous levosimendan in healthy Chinese volunteers and ethnic comparisons

Kai Min Chu, Oliver Yoa Pu Hu, Jun Ting Liou

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)298-307
Number of pages10
JournalActa Cardiologica Sinica
Volume30
Issue number4
Publication statusPublished - Jan 1 2014
Externally publishedYes

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Healthy Volunteers
Pharmacokinetics
Area Under Curve
Half-Life
simendan
Intravenous Infusions
Echocardiography
High Pressure Liquid Chromatography

Keywords

  • Chinese
  • Ethnic comparison
  • Levosimendan
  • Pharmacodynamics
  • Pharmacokinetics
  • Volunteer

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

A pharmacokinetic and pharmacodynamic study of intravenous levosimendan in healthy Chinese volunteers and ethnic comparisons. / Chu, Kai Min; Hu, Oliver Yoa Pu; Liou, Jun Ting.

In: Acta Cardiologica Sinica, Vol. 30, No. 4, 01.01.2014, p. 298-307.

Research output: Contribution to journalArticle

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abstract = "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.",
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