Hematology, Hemostasis, Oncology and Stem Cell Transplantation Unit, Hannover Medical School, Hannover, Germany.
Thrombosis and Haemostasis Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
Thromb Haemost. 2020 Feb;120(2):277-288. doi: 10.1055/s-0039-3400745. Epub 2019 Dec 30.
Factor VIII (FVIII) products are usually dosed according to body weight (BW). This may lead to under- or over-dosing in underweight or obese patients, respectively.
This article evaluates the pharmacokinetics (PK) of recombinant FVIII concentrate, particularly recovery, in relation to body mass index (BMI) and other body composition descriptors.
Thirty-five previously treated adults with severe haemophilia A from five BMI categories (underweight, normal, overweight, obese class I and II/III) were included. PK was evaluated after 50 IU per kilogram of BW single-dose recombinant FVIII (turoctocog alfa). The body composition variable was based on measurements of weight, height, bioimpedance analysis, and dual-energy X-ray absorptiometry. A dosing model was derived to achieve similar peak FVIII activity levels across BMI categories.
A statistically significant positive association between BMI and C, IR, and AUC was observed; CL and V showed a significant negative association with BMI; t was independent of BMI and other parameters. The dosing model introduced a correction factor 'M' for each BMI category, based on linear regression analysis of C against BMI, which ranged from 0.55 for underweight to 0.39 for obese class II/III. This model achieved similar peak FVIII activity levels across BMI categories, estimating an average dose adjustment of +243.3 IU (underweight) to -1,489.6 IU (obese class II/III) to achieve similar C.
BMI appears to be the best predictor of recombinant FVIII recovery; however, PK endpoints were also dependent on other body composition variables. The model demonstrated that dosing can be adjusted for individual BMI to achieve better FVIII predictability across BMI categories.
VIII 因子（FVIII）产品通常根据体重（BW）给药。这可能分别导致体重不足或肥胖患者的用药不足或过量。
本文评估了重组 FVIII 浓缩物的药代动力学（PK），特别是与体重指数（BMI）和其他身体成分指标相关的恢复情况。
纳入了来自五个 BMI 类别（体重不足、正常、超重、肥胖 I 类和 II/III 类）的 35 名先前接受过治疗的严重血友病 A 成人患者。在 50IU/kg BW 单剂量重组 FVIII（turoctocog alfa）后评估 PK。身体成分变量基于体重、身高、生物阻抗分析和双能 X 射线吸收法测量。推导了一个剂量模型，以在 BMI 类别中实现相似的峰值 FVIII 活性水平。
观察到 BMI 与 C、IR 和 AUC 呈显著正相关；CL 和 V 与 BMI 呈显著负相关；t 与 BMI 及其他参数无关。该剂量模型为每个 BMI 类别引入了一个校正因子“M”，基于 C 与 BMI 的线性回归分析，范围从体重不足的 0.55 到肥胖 II/III 类的 0.39。该模型在 BMI 类别中实现了相似的峰值 FVIII 活性水平，估计平均剂量调整为+243.3IU（体重不足）至-1489.6IU（肥胖 II/III 类）以达到相似的 C。
BMI 似乎是重组 FVIII 恢复的最佳预测指标；然而，PK 终点也依赖于其他身体成分变量。该模型表明，剂量可以根据个体 BMI 进行调整，以在 BMI 类别中实现更好的 FVIII 可预测性。
