Hemophilia A is a rare bleeding disorder resulting from a lack of functional factor VIII (FVIII). Therapy consists of replacement with exogenous FVIII, but is complicated by high inter-patient variability. A population pharmacokinetics (PopPK) approach can facilitate the uptake of an individualized approach to hemophilia therapy. We developed a PopPK model using data from seven brands of standard half-life FVIII products. The final model consists of a 2-compartment structure, with a proportional residual error model and between-subject variability on clearance and central volume. Fat-free mass, age, and brand were found to significantly affect pharmacokinetic (PK) parameters. Internal and external evaluations found that the model is fit for Bayesian forecasting and capable of predicting PK for brands not included in the modelling dataset, and useful for determining individualized prophylaxis regimens for hemophilia A patients.

中文翻译：

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开发和评估用于剂量个体化的标准半衰期因子VIII的通用人群药代动力学模型。

甲型血友病是由于缺乏功能性因子VIII（FVIII）而引起的罕见出血性疾病。治疗包括用外源性FVIII替代，但因患者之间的高变异性而变得复杂。群体药代动力学（PopPK）方法可以促进采用个体化方法进行血友病治疗。我们使用来自七个品牌的标准半衰期FVIII产品的数据开发了PopPK模型。最终模型由2隔室结构组成，具有成比例的残差模型和间隙和中心容积之间的对象间差异。发现无脂脂肪的质量，年龄和品牌会显着影响药代动力学（PK）参数。内部和外部评估发现，该模型适合贝叶斯预测，并且能够预测未包含在建模数据集中的品牌的PK，