Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice
Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice
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DOI：
10.1038/aps.2015.121
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发表时间：
2016-03-01
影响因子：
8.2
通讯作者：
Dou, Gui-fang
中科院分区：
文献类型：
--
作者：
Gu, Ruo-lan;Liu, Liang;Dou, Gui-fang
目的：SCT 800是一种新的第三代重组FVIII制剂，正在进行有前途的临床前研究。方法：血友病A小鼠单次静脉注射SCT 800（80、180和280 IU/kg）或市售产品Xyntha（280 IU/kg）后，通过测定血浆FVIII：C，评价SCT 800在血友病A小鼠体内的药代动力学和药效学特征。结果：SCT 800在80 ~ 280 IU/kg剂量范围内与Xyntha的药代动力学曲线基本一致，且SCT 800与Xyntha的药代动力学曲线具有剂量依赖性。药效学研究显示，在尾部出血模型中，SCT 800和Xyntha的ED 50值相当：出血时间分别为14.78和15.81 IU/kg;失血量分别为13.50和13.58 IU/kg。此外，在测试的剂量，伴随的剂量相关的安全性评价在尾部出血模型显示较低的高凝倾向和更广泛的剂量范围潜力SCT 800比Xyntha.Conclusion：在血友病A小鼠，SCT 800显示可比的药代动力学和药效学Xyntha在测试的剂量，并可能具有更好的安全性。
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.