Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, OH, USA.
J Thromb Haemost. 2014 Dec;12(12):2038-43. doi: 10.1111/jth.12739. Epub 2014 Oct 25.
The use of monthly recombinant factor XIII (rFXIII) recently demonstrated favorable safety and efficacy for congenital FXIII A-subunit deficiency patients aged ≥ 6 years (mentor(™) 1 trial), although the pharmacokinetics (PK) were not fully evaluated.
To comprehensively evaluate the steady-state PK of rFXIII in patients aged ≥ 6 years with congenital FXIII A-subunit deficiency.
PATIENTS/METHODS: mentor(™) 2 is an ongoing, multinational safety and efficacy trial in which patients are receiving monthly rFXIII (35 IU kg(-1) ) for ≥ 52 weeks. For this 28-day PK analysis, blood samples were collected immediately predosing, and 1 h, 2 h, 3, 7, 14, 21, and 28 days postdosing. FXIII activity was measured and PK parameters were calculated using non-compartmental analysis, without prior baseline adjustment. Information regarding adverse events and bleeding was collected at each visit. Antibody assessments were performed predosing and at day 28.
PK analysis in 23 patients revealed first-order elimination of rFXIII with a geometric mean half-life of 13.6 days. Mean FXIII activity was > 0.1 IU mL(-1) throughout the 28-day period, with a geometric mean peak activity of 0.87 IU mL(-1) and trough of 0.16 IU mL(-1) . The geometric mean clearance was 0.15 mL h(-1) kg(-1) . No bleeding episodes occurred during the PK session, and no anti-rFXIII antibodies were detected. Peak and trough FXIII activities were constant over time, compared with previous activities (≥ 10 rFXIII doses) in the same patients.
Clearance of rFXIII is unaffected over time, and monthly prophylaxis with 35 IU kg(-1) rFXIII provides FXIII activity > 0.1 IU mL(-1) throughout the dosing interval in patients with congenital FXIII A-subunit deficiency.
最近，每月重组凝血因子 XIII（rFXIII）的使用对年龄≥6 岁的先天性 FXIII A 亚单位缺乏症患者显示出良好的安全性和疗效（mentor(™)1 试验），尽管尚未充分评估其药代动力学（PK）。
全面评估年龄≥6 岁的先天性 FXIII A 亚单位缺乏症患者使用 rFXIII 的稳态 PK。
患者/方法：mentor(™)2 是一项正在进行的、多中心的安全性和疗效试验，其中患者接受每月 35 IU kg(-1)rFXIII 治疗≥52 周。在本次 28 天 PK 分析中，在给药前即刻、给药后 1 小时、2 小时、3 小时、7 小时、14 天、21 天和 28 天采集血样。使用非房室分析测量 FXIII 活性并计算 PK 参数，无需预先进行基线调整。在每次就诊时收集关于不良事件和出血的信息。在给药前和第 28 天进行抗体评估。
对 23 名患者的 PK 分析显示 rFXIII 的消除呈一级动力学，几何平均半衰期为 13.6 天。在整个 28 天期间，平均 FXIII 活性>0.1 IU mL(-1)，几何平均峰值活性为 0.87 IU mL(-1)，谷值为 0.16 IU mL(-1)。几何平均清除率为 0.15 mL h(-1) kg(-1)。在 PK 期间未发生出血事件，也未检测到抗-rFXIII 抗体。与同一患者之前的（≥10 次 rFXIII 剂量）活性相比，峰值和谷值 FXIII 活性随时间保持稳定。
rFXIII 的清除率随时间保持不变，每月 35 IU kg(-1)rFXIII 预防性给药可在先天性 FXIII A 亚单位缺乏症患者的整个给药间隔内提供 FXIII 活性>0.1 IU mL(-1)。
