Background: Although much attention has been paid to the pharmacokinetics (PKs) of different factor VIII (FVIII) concentrates in persons with hemophilia A (HA), limited information is available in young boys with severe HA. In this study, we aimed to assess the PK parameters of FVIII products in boys with severe HA in China.
Methods: A total of 36 boys (plasma-derived [pd]-FVIII, n = 15; recombinant [r] FVIII, n = 21) were enrolled between January 2015 and May 2016 in Beijing Children's Hospital. PK characteristics of FVIII products were studied according to a reduced 4-sampling time point design (1 h, 9 h, 24 h, and 48 h postinfusion).
Results: The mean FVIII half-life (t1/2) was 10.99 ± 3.45 h (range 5.52-20.02 h), the mean in vivo recovery (IVR) was 2.01 ± 0.42 IU/dl per IU/kg (range 1.24-3.02 IU/dl per IU/kg) and mean clearance (CL) of FVIII is 4.34 ± 1.58 ml·kg-1·h-1 (range 2.29-7.90 ml·kg-1·h-1). We also analyzed the influence of several parameters that potentially modulate FVIII PK. The age was closely associated with FVIII half-life (R2 = 0.32, P < 0.01). The t1/2of FVIII increased by 0.59 h per year. Besides age, von Willebrand factor antigen (VWF:Ag) also was associated with FVIII half-life (R2 = 0.52, P < 0.01). Patients with blood Group O had a shorter FVIII half-life than patients with non-O blood group (9.40 ± 0.68 h vs. 12.3 ± 0.79 h, t = 2.70, P = 0.01). The FVIII IVR correlated with age (R2 = 0.21, P < 0.01) and VWF:Ag level (R2 = 0.28, P < 0.01). CL rates were faster in young patients and in those with low-VWF:Ag levels. CL rates of FVIII are higher in blood Group O versus non-blood Group O persons (5.02 ± 0.38 vs. 4.00 ± 0.32 ml·kg-1·h-1, t = 2.53, P = 0.02).
Conclusions: Chinese boys with severe HA have similar PK values to other ethnic groups and large differences in FVIII PK between individual patients. Age, blood group, and VWF:Ag levels are important determining factors for FVIII CL.
中国重型血友病儿童的FⅧ药代动力学特征：一项单中心研究摘要背景：关于血友病患者的FⅧ的药代动力学（PK）研究有很多，但是针对儿童重型血友病患者的FⅧ药代动力学研究很少。本研究旨在评估FⅧ在中国重型血友病患儿中的药代动力学特征。 方法：自2015年2月至2016年5月共纳入36例符合入组标准的重型血友病患儿（其中15例应用血浆来源的FⅧ治疗，21例应用重组的FⅧ治疗）。运用减量样本4个采样时间点（输注FⅧ后1小时、9小时、24小时、48小时）的PK检测方案对FⅧ的PK特征进行研究。 结果： FⅧ的半衰期为10.99 ± 3.45h (范围5.52-20.02 h)，平均体外回收率为2.01± 0.42 IU/dl per IU/kg (范围1.24-3.02 IU/dl per IU/kg)，平均清除率为4.34 ±1.58 ml·kg-1·h-1(范围 2.29-7.90 ml·kg-1·h-1)。我们同时分析了PK的影响因素，研究结果显示FⅧ的半衰期与年龄显著相关(R2=0.32, P <0.01)，年龄每增长1岁，半衰期延长0.59小时。除年龄外，VWF抗原水平也与FⅧ半衰期密切相关(R2=0.52, P <0.01)。FⅧ在O型血患者的半衰期显著低于非O型血患者（9.40 ± 0.68 h vs. 12.3 ± 0.79h, t=2.70, P =0.01)。FⅧ的体内回收率与年龄、VWF抗原水平相关(相关系数分别为R2=0.21、0.28, P均<0.01)。低年龄患儿及VWF抗原水平的患儿其FⅧ清除速率加快。O型血患者体内的FⅧ清除率高于非O型血患者（5.02±0.38 vs.4.00±0.32 ml·kg-1·h-1, t=2.53, P=0.02）。 结论：中国重型血友病儿童FⅧ的药代动力学特征与其他种族的特征相似。不同个体间的FⅧ药代动力学参数差异较大，年龄、血型及VWF抗原水平是影响FⅧ清除的重要因素。.
Keywords: Boys; Factor VIII; Hemophilia A; Pharmacokinetics.