title: Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice.
abstract: OBJECTIVE
  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
  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.
  
  
  CONCLUSIONS
  In hemophilia A mice, SCT800 shows comparable pharmacokinetics and pharmacodynamics to Xyntha at the doses tested, and possibly with better safety properties.
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Ruo-lan
authors.initials: RL
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Cell Culture R&D Center, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Liang-zhi
authors.initials: LZ
authors.lastname: Xie
authors.affiliation: Cell Culture R&D Center, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Wen-lin
authors.initials: WL
authors.lastname: Gai
authors.affiliation: Cell Culture R&D Center, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Si-shuo
authors.initials: SS
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Zhi-yun
authors.initials: ZY
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gan
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Zhuo-na
authors.initials: ZN
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Xiao-xia
authors.initials: XX
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Gui-fang
authors.initials: GF
authors.lastname: Dou
mesh_terms: D000818:Animals; D005169:Factor VIII / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy*; D006470:Hemorrhage / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII