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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pharmacokinetics and pharmacodynamics of simendan, a novel calcium sensitizer, in healthy volunteers.

OBJECTIVE: To assess pharmacokinetics and correlation of pharmacokinetics and pharmacodynamics of simendan, a new calcium-sensitizing compound aimed at the treatment of congestive heart failure, in healthy volunteers. METHODS: Simendan was administered to eight healthy subjects in seven different doses, and its concentrations in plasma and proportions of enantiomers (levosimendan and dextrosimendan) were determined. Hemodynamic effects were measured by M-mode echocardiography. RESULTS: The area under the plasma concentration time-curve increased linearly and correlated with dose (p < 0.001). The volumes of distribution were small (mean VC, 8.5 to 14.1 L; VSS, 12.8 to 28.4 L) and elimination fairly fast (mean t1/2 beta, 0.83 to 1.77 hours). There were only minor differences between the pharmacokinetic profiles of the enantiomers of simendan. The increase in maximal ejection fraction (EF) correlated significantly with the plasma concentrations of simendan (p < 0.01; r2 = 0.33). However, the correlation coefficient was higher between estimated concentrations of simendan in peripheral compartment and ejection fraction; r2 was 0.79 (p < 0.01) and 0.94 (p < 0.001) after 2 and 5 mg doses, respectively. One subject after 5 mg simendan and one subject after 10 mg simendan had transient vasovagal reactions consisting of decreases in heart rate and blood pressure. CONCLUSIONS: Simendan has favorable and predictable hemodynamic actions. The pharmacokinetic profile facilitates rapid dose adjustments during intravenous administration.[1]


  1. Pharmacokinetics and pharmacodynamics of simendan, a novel calcium sensitizer, in healthy volunteers. Lilleberg, J., Antila, S., Karlsson, M., Nieminen, M.S., Pentkäinen, P.J. Clin. Pharmacol. Ther. (1994) [Pubmed]
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