The features of clearance in recombinant factor IX (BeneFIX).
The features of clearance in recombinant factor IX (BeneFIX).
复制标题
重组因子 IX (BeneFIX) 的清除特征。
DOI：
10.1111/hae.12672
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Matsushita T.
中科院分区：
文献类型：
--
作者：
Suzuki N;Takedani H;Hirakawa A;Ushijima Y;Matsushita T.
为了更有效、更经济地持续输注重组凝血因子IX（rFIX），剂量调整是非常重要的，而清除率（CL）与输注速率密切相关。然而，先前的报告表明，rFIX浓缩物的CL差异很大（4.2-11.4 mL kg−1h−1）。目的本研究的目的是更好地了解rFIX浓缩物的CL（BeneFIX®）来精确地设定rFIX浓缩物的输注速率。根据血药浓度-时间曲线下面积（AUC），根据体内恢复（IVR）和半衰期，根据CI期间的实际FIX活性值，7例血友病B患者的一室模型模拟结果。结果根据AUC计算的平均CL为3.8 ± 0.4 mL kg−1h−1（范围= 3.3-4.3 mL kg−1h−1）。结论根据IVR和分布半衰期计算的平均CL为4.4 ± 0.4 mL kg−1h−1（范围= 4.0-5.1 mL kg−1h−1）。根据IVR和终末半衰期计算的平均CL为2.1 ± 0.5 mL kg−1h−1（范围= 1.7-2.8 mL kg−1h−1）。CI期间的平均CL为4.9 ± 0.6 mL kg−1h−1（范围= 4.2-5.6 mL kg−1h−1）。此外，当我们使用一室模型模拟理论CL时，CI期间的校正平均CL为4.8 ± 0.5 mL kg−1h−1（范围= 4.0-5.4 mL kg−1h−1）。根据分布半衰期获得的CL与CI期间的CL相当，而根据终末半衰期计算的CL并不反映实际CL。此外，在某些条件下，rFIX浓缩液的特征为一室模型。
IntroductionDosage adjustment is very important to perform continuous infusion (CI) of recombinant factor IX (rFIX) concentrates more effectively and economically, and clearance (CL) is strongly related to the infusion rate. However, previous reports have shown that the CL of rFIX concentrates varies widely (4.2–11.4 mL kg−1h−1).AimThe goal of this study was to gain a better understanding of the CL of the rFIX concentrate (BeneFIX®) to precisely set the infusion rate of rFIX concentrates.MethodsWe estimated CLs by five different calculation approaches: from area under the blood concentration–time curve (AUC), fromin vivorecovery (IVR) and half‐life, from actual FIX activity value during CI, and from the simulation by one‐compartment model in seven patients with haemophilia B.ResultsThe mean CL calculated from AUC was 3.8 ± 0.4 mL kg−1h−1(range = 3.3–4.3 mL kg−1h−1).ConclusionThe mean CL calculated from IVR and distribution half‐life was 4.4 ± 0.4 mL kg−1h−1(range = 4.0–5.1 mL kg−1h−1). The mean CL calculated from IVR and terminal half‐life was 2.1 ± 0.5 mL kg−1h−1(range = 1.7–2.8 mL kg−1h−1). The mean CL during CI was 4.9 ± 0.6 mL kg−1h−1(range = 4.2–5.6 mL kg−1h−1). In addition, when we simulated the theoretical CL using a one‐compartment model, the adjusted mean CL during CI was 4.8 ± 0.5 mL kg−1h−1(range = 4.0–5.4 mL kg−1h−1). The CL obtained from distribution half‐life was comparable to the CL during CI, while the CL calculated from terminal half‐life did not reflect actual CL. Further, the rFIX concentrate was characterized by a one‐compartment model under certain conditions.