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Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice

  
@article{APS9448,
	author = {Ruo-lan GU and Liang LIU and Liang-zhi XIE and Wen-lin GAI and Si-shuo CAO and Zhi-yun MENG and Hui GAN and Zhuo-na WU and Jian LI and Ying ZHENG and Xiao-xia ZHU and Gui-fang DOU},
	title = {Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice},
	journal = {Acta Pharmacologica Sinica},
	volume = {37},
	number = {3},
	year = {2017},
	keywords = {},
	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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/9448}
}