CHU Besançon, Laboratoire de Pharmacologie Clinique, Hôpital Jean Minjoz, Besançon, France.
Br J Cancer. 2010 Mar 2;102(5):827-32. doi: 10.1038/sj.bjc.6605560. Epub 2010 Feb 16.
HuHMFG1 (AS1402) is a humanised monoclonal antibody that has undergone a phase I trial in metastatic breast cancer. The aim of this study was to characterise the pharmacokinetics (PKs) of HuHMFG1 using a population PK model.
Data were derived from a phase I study of 26 patients receiving HuHMFG1 at doses ranging from 1 to 16 mg kg(-1). Data were analysed using NONMEM software and covariates were included. A limited sampling strategy (LSS) was developed using training and a validation data set.
A linear two-compartment model was shown to be adequate to describe data. Covariate analysis indicated that weight was not related to clearance. An LSS was successfully developed on the basis of the model, in which one sample is collected immediately before the start of an infusion and the second is taken at the end of infusion.
A two-compartment population PK model successfully describes HuHMFG1 behaviour. The model suggests using a fixed dose of HuHMFG1, which would simplify dosing. The model could be used to optimise dose level and dosing schedule if more data on the correlation between exposure and efficacy become available from future studies. The derived LSS could optimise further PK assessment of this antibody.
HuHMFG1（AS1402）是一种人源化单克隆抗体，已在转移性乳腺癌的 I 期临床试验中进行了研究。本研究的目的是使用群体药代动力学（PK）模型来描述 HuHMFG1 的药代动力学（PK）特征。
数据来自 26 例接受 HuHMFG1 剂量为 1 至 16mg/kg 的 I 期研究。数据分析采用 NONMEM 软件，并包括协变量。使用训练集和验证数据集开发了有限采样策略（LSS）。
线性二室模型被证明足以描述数据。协变量分析表明，体重与清除率无关。在此模型基础上成功开发了 LSS，其中一个样本在输注开始前立即采集，第二个样本在输注结束时采集。
成功建立了描述 HuHMFG1 行为的两室群体 PK 模型。该模型提示使用固定剂量的 HuHMFG1，这将简化给药方案。如果未来研究获得更多关于暴露量与疗效之间相关性的更多数据，该模型可用于优化剂量水平和给药方案。所推导的 LSS 可以进一步优化对这种抗体的 PK 评估。
