Abstract
Aim:
SCT800 is a new third-generation recombinant FVIII agent that is undergoing promising preclinical study. This study aimed to investigate the pharmacokinetic and pharmacodynamic profiles of SCT800 in hemophilia A mice.
Methods:
After hemophilia A mice were intravenously injected with single dose of SCT800 (80, 180, and 280 IU/kg) or the commercially available product Xyntha (280 IU/kg), pharmacokinetics profiles were evaluated based on measuring plasma FVIII: C. For pharmacodynamics study, dose-response curves of SCT800 and Xyntha (1–200 IU/kg) were constructed using a tail bleeding model monitoring both bleeding time and blood loss.
Results:
Pharmacokinetics profile analysis showed a dose independency of SCT800 ranging from 80 to 280 IU/kg and comparable pharmacokinetic profiles between SCT800 and Xyntha at the doses tested. Pharmacodynamics study revealed comparable ED50 values of SCT800 and Xyntha in the tail bleeding model: 14.78 and 15.81 IU/kg for bleeding time, respectively; 13.50 and 13.58 IU/kg for blood loss, respectively. Moreover, at the doses tested, the accompanying dose-related safety evaluation in the tail bleeding model showed lower hypercoagulable tendency and wider dosage range potential for SCT800 than Xyntha.
Conclusion:
In hemophilia A mice, SCT800 shows comparable pharmacokinetics and pharmacodynamics to Xyntha at the doses tested, and possibly with better safety properties.
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Acknowledgements
This work was supported by the National Science and Technology Key Projects for Major New Drugs Innovation and Development (No 2011ZX09202-301-10) and the National Natural Science Foundation of China (No 21104095).
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Gu, Rl., Liu, L., Xie, Lz. et al. Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice. Acta Pharmacol Sin 37, 408–414 (2016). https://doi.org/10.1038/aps.2015.121
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DOI: https://doi.org/10.1038/aps.2015.121
