Hospital Pharmacy-Clinical Pharmacology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Thromb Haemost. 2021 Jun;121(6):731-740. doi: 10.1055/s-0040-1721484. Epub 2021 Jan 27.
The pharmacokinetic (PK) properties of extended half-life (EHL) factor VIII (FVIII) concentrates differ, leading to variation in the optimal dosing regimen for the individual patient. The aim of this study was to establish these PK differences for various EHL FVIII concentrates by in silico simulations.
FVIII level over time profiles of rFVIII-SC, BAY 81-8973, rFVIII-Fc, BAX 855, BAY 94-9027, and standard half-life (SHL) rFVIII concentrates were simulated for 1,000 severe hemophilia A patients during steady-state dosing of 40 IU/kg every 72 hours or dosing as advised in the summary of product characteristics (SmPC).
Although the elimination half-life values were comparable for rFVIII-FC, BAX 855, and BAY 94-9027, a higher area under the curve (AUC; 2,779 IU/h/dL) for BAY 94-9027 was obtained. During steady-state dosing of 40 IU/kg every 72 hours, 58.5% (rFVIII-SC), 69.3% (BAY 81-8972), 89.0% (rFVIII-Fc), 83.9% (BAX 855), and 93.7% (BAY 94-9027) of the patients maintained a trough level of 1 IU/dL, compared with 56.0% for SHL rFVIII. Following dosing schemes described in the SmPC, between 51.0 and 65.4% or 23.2 and 31.1% of the patients maintained a target trough level of 1 IU/dL or 3 IU/dL, respectively.
BAY 94-9027 showed the largest increase of AUC and best target attainment compared with SHL rFVIII, followed closely by BAX 855 and rFVIII-Fc. BAY 81-8973 and rFVIII-SC showed smaller PK improvements. Although our analyses increase insight into the PK of these FVIII concentrates, more studies evaluating the relation between factor levels and bleeding risk are needed.
具有延长半衰期（EHL）的因子 VIII（FVIII）浓缩物的药代动力学（PK）特性不同，导致个体患者的最佳给药方案存在差异。本研究旨在通过计算机模拟确定各种 EHL FVIII 浓缩物的这些 PK 差异。
对 rFVIII-SC、BAY 81-8973、rFVIII-Fc、BAX 855、BAY 94-9027 和标准半衰期（SHL）rFVIII 浓缩物的 1000 名重度 A 型血友病患者在稳态下每 72 小时给予 40IU/kg 或根据产品特性摘要（SmPC）建议进行给药的情况下，FVIII 水平随时间的变化进行了模拟。
尽管 rFVIII-Fc、BAX 855 和 BAY 94-9027 的消除半衰期值相当，但 BAY 94-9027 的 AUC（2779IU/h/dL）更高。在每 72 小时给予 40IU/kg 的稳态剂量下，58.5%（rFVIII-SC）、69.3%（BAY 81-8972）、89.0%（rFVIII-Fc）、83.9%（BAX 855）和 93.7%（BAY 94-9027）的患者维持 1IU/dL 的谷水平，而 SHL rFVIII 为 56.0%。按照 SmPC 中描述的给药方案，分别有 51.0%至 65.4%或 23.2%至 31.1%的患者维持 1IU/dL 或 3IU/dL 的目标谷水平。
BAY 94-9027 与 SHL rFVIII 相比，AUC 增加最大，目标达标率最高，其次是 BAX 855 和 rFVIII-Fc。BAY 81-8973 和 rFVIII-SC 显示出较小的 PK 改善。尽管我们的分析增加了对这些 FVIII 浓缩物 PK 的了解，但仍需要更多研究来评估因子水平与出血风险之间的关系。
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