Teitel Jerome, Sholzberg Michelle, Iorio Alfonso
Department of Medicine St. Michael's Hospital University of Toronto Toronto ON Canada.
Departments of Medicine and Laboratory Medicine and Pathobiology St. Michael's Hospital University of Toronto Toronto ON Canada.
Res Pract Thromb Haemost. 2021 Feb 23;5(2):349-355. doi: 10.1002/rth2.12476. eCollection 2021 Feb.
The use of pharmacokinetic (PK) studies to help design personalized prophylaxis regimens for factor VIII (FVIII) concentrate in individuals with hemophilia A has been recognized for many years but only became practical for routine clinical use with the availability of web-accessible population PK applications based on Bayesian analysis.
To compare PK variables using population PK studies done on 2 extended half-life recombinant FVIII concentrates in 23 individuals with hemophilia A after switching from one product to the other.
We retrospectively analyzed PK parameters derived from the Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-HEMO) application on 23 individuals with severe or moderately severe hemophilia A who were required to switch from recombinant FVIII Fc (Eloctate; Biogen, Cambridge, MA, USA) to recombinant antihemophilic factor PEGylated (Adynovate; Takeda Pharmaceutical Company, Osaka, Japan) between 2016 and 2017.
There were minor PK differences between Eloctate and Adynovate, but some parameters did reach statistical significance, namely in vivo recovery (mean, 2.73 IU/dL per IU/kg vs 2.41 IU/dL per IU/kg), clearance (mean, 0.163 mL/h vs 0.194 mL/h), and volume of distribution at steady state (mean, 42.5 ml/kg vs 49.8 mL/kg). Smaller nonsignificant trends toward higher values for Adynovate were seen in terminal half-life, area under the curve, and predicted times to 5% and 1% residual FVIII after infusion.
Population PK analysis revealed differences between the two extended half-life FVIII concentrates, reaching significance for in vivo recovery, clearance, and volume of distribution.
多年来，利用药代动力学（PK）研究来帮助设计针对甲型血友病患者的凝血因子VIII（FVIII）浓缩物个性化预防方案已得到认可，但随着基于贝叶斯分析的可网络访问的群体PK应用程序的出现，这才在常规临床应用中变得切实可行。
在23例甲型血友病患者从一种产品转换为另一种产品后，使用群体PK研究比较两种延长半衰期重组FVIII浓缩物的PK变量。
我们回顾性分析了来自网络可访问群体药代动力学服务-血友病（WAPPS-HEMO）应用程序的PK参数，该应用程序涉及23例重度或中度重度甲型血友病患者，他们在2016年至2017年间从重组FVIII Fc（Eloctate；美国马萨诸塞州剑桥市百健公司）转换为聚乙二醇化重组抗血友病因子（Adynovate；日本大阪武田制药公司）。
Eloctate和Adynovate之间存在轻微的PK差异，但一些参数确实具有统计学意义，即体内回收率（平均值，每IU/kg为2.73 IU/dL对每IU/kg为2.41 IU/dL）、清除率（平均值，0.163 mL/h对0.194 mL/h）和稳态分布容积（平均值，42.5 ml/kg对49.8 mL/kg）。在终末半衰期、曲线下面积以及输注后FVIII残留量达到5%和1%的预测时间方面，Adynovate有较小的、无统计学意义的更高值趋势。
群体PK分析揭示了两种延长半衰期FVIII浓缩物之间的差异，在体内回收率、清除率和分布容积方面具有统计学意义。
