Fanhdi/Alphanate is a plasma derived factor VIII concentrate used for treating hemophilia A, for which there has not been any dedicated model describing its pharmacokinetics (PK). A population PK model was developed using data extracted from the Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) project. WAPPS-Hemo provided individual PK profiles for hemophilia patients using sparse observations as provided in routine clinical care by hemophilia centers. Plasma factor activity measurements and covariate data from hemophilia A patients on Fanhdi/Alphanate were extracted from the WAPPS-Hemo database. A population PK model was developed using NONMEM and evaluated for suitability for Bayesian forecasting using prediction-corrected visual predictive check (pcVPC), cross validation, limited sampling analysis and external evaluation against a population PK model developed on rich sampling data. Plasma factor activity measurements from 92 patients from 12 centers were used to derive the model. The PK was best described by a 2-compartment model including between subject variability on clearance and central volume, fat free mass as a covariate on clearance, central and peripheral volumes, and age as covariate on clearance. Evaluations showed that the developed population PK model could predict the PK parameters of new individuals based on limited sampling analysis and cross and external evaluations with acceptable precision and bias. This study shows the feasibility of using real-world data for the development of a population PK model. Evaluation and comparison of the model for Bayesian forecasting resulted in similar results as a model developed using rich sampling data.

中文翻译：

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用于群体药代动力学建模的常规临床护理数据：A型血友病患者中的Fanhdi / Alphanate病例。

Fanhdi / Alphanate是血浆衍生的VIII因子浓缩物，用于治疗A型血友病，目前尚无任何专门模型描述其药代动力学（PK）。人口PK模型是使用从可访问网络的人口药代动力学服务-血友病（WAPPS-Hemo）项目中提取的数据开发的。WAPPS-Hemo使用血友病中心常规临床护理中提供的稀疏观察，为血友病患者提供了个人PK资料。来自血友病的血浆因子活性测量值和协变量数据从WAPPS-Hemo数据库中提取Fanhdi / Alphanate上的A例患者。使用NONMEM开发了总体PK模型，并使用预测校正的视觉预测检查（pcVPC），交叉验证，针对基于丰富采样数据开发的总体PK模型进行的有限采样分析和外部评估。使用来自12个中心的92位患者的血浆因子活性测量值来得出模型。PK最好由2室模型描述，包括受试者清除率和中心体积的变异性，无脂肪量作为清除率的协变量，中央和周围体积以及年龄作为清除率的协变量之间的差异。评价表明，基于有限的抽样分析以及具有可接受的精度和偏差的交叉和外部评估，发达的人口PK模型可以预测新个体的PK参数。这项研究显示了使用真实数据开发人口PK模型的可行性。