Allometric Scaling of Therapeutic Monoclonal Antibodies Using Antigen Concentration as a Correction Factor: Application to the Human Clearance Prediction

异速滴定 单克隆抗体 缩放比例 动物种类 抗原 贝伐单抗 抗体 计算生物学 化学 生物 数学 免疫学 医学 内科学 生态学 动物 几何学 化疗
作者
Lei Wang,Wei Qiang,Zeneng Cheng
出处
期刊:Journal of Pharmaceutical Sciences [Elsevier BV]
卷期号:105 (3): 1335-1340 被引量:7
标识
DOI:10.1016/j.xphs.2015.12.021
摘要

Allometric scaling has been widely used for predictions of human pharmacokinetic (PK) parameters in the development of monoclonal antibody (mAb) drugs, and some correction factors have been proposed to improve the estimations. However, classic correction factors fail to offer a complete explanation of the additional differences among species besides the body weight and, thus, lack enough power to further improve the predictions. In this study, the antigen concentration was initially set as a new correction factor to predict the human clearance (CL) of mAbs. Bevacizumab was intravenously injected into 2 animal species and humans to obtain PK data to predict human CL from the animal data. Additionally, a new approach was also validated with data from 3 other mAbs which were collected through a literature review of published work. Accordingly, allometric scaling with a correction factor of the antigen concentration generated accurate estimations of the human CL of 4 mAbs, which were superior to the results obtained by other classic scaling methods. More importantly, the proposed method also achieved good predictions of individual human CL of bevacizumab. In conclusion, the potential of this method as a powerful tool for human PK estimation of mAbs in species translation has been demonstrated.
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