TY - JOUR AU - GU Ruo-lan AU - LIU Liang AU - XIE Liang-zhi AU - GAI Wen-lin AU - CAO Si-shuo AU - MENG Zhi-yun AU - GAN Hui AU - WU Zhuo-na AU - LI Jian AU - ZHENG Ying AU - ZHU Xiao-xia AU - DOU Gui-fang PY - 2017 TI - Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice JF - Acta Pharmacologica Sinica; Vol 37, No 3 (March 2016): Acta Pharmacologica Sinica Y2 - 2017 KW - N2 - 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 ED 50 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. UR - http://www.chinaphar.com/article/view/9448