Back to Search
Start Over
Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice.
- Source :
-
Acta pharmacologica Sinica [Acta Pharmacol Sin] 2016 Mar; Vol. 37 (3), pp. 408-14. Date of Electronic Publication: 2016 Jan 25. - Publication Year :
- 2016
-
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.<br />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<br />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.<br />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.<br />Conclusion: In hemophilia A mice, SCT800 shows comparable pharmacokinetics and pharmacodynamics to Xyntha at the doses tested, and possibly with better safety properties.
- Subjects :
- Animals
Factor VIII pharmacology
Female
Hemophilia A complications
Hemorrhage complications
Male
Mice
Mice, Inbred C57BL
Recombinant Proteins pharmacokinetics
Recombinant Proteins pharmacology
Recombinant Proteins therapeutic use
Factor VIII pharmacokinetics
Factor VIII therapeutic use
Hemophilia A drug therapy
Hemorrhage drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1745-7254
- Volume :
- 37
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Acta pharmacologica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- 26806305
- Full Text :
- https://doi.org/10.1038/aps.2015.121