A systematic review of allometric scaling exponents for IgG mAbs

Increasing complexity of mAbs in development creates challenges in predicting human pharmacokinetic (PK) parameters from preclinical data. The aim of this analysis was to identify optimal allometric scaling exponents.Data were extracted from literature to create a central database (currently the largest available published database) of two-compartment model parameters for mAbs (<i>n</i> = 59) in cynomolgus monkey (CM) and human.Global allometric exponents were calculated and drug-dependent factors were investigated as potential variables in determining the optimal scaling factor.The global exponents for scaling CM mAb PK data were 0.74 (CL), 0.80 (CL with Fc-modified mAbs excluded), 0.44 (CL with Fc-modified mAbs only), 0.71 (Q), 1.12 (V1), and 0.99 (V2). These values are in line with previously published literature values. Increasing complexity of mAbs in development creates challenges in predicting human pharmacokinetic (PK) parameters from preclinical data. The aim of this analysis was to identify optimal allometric scaling exponents. Data were extracted from literature to create a central database (currently the largest available published database) of two-compartment model parameters for mAbs (<i>n</i> = 59) in cynomolgus monkey (CM) and human. Global allometric exponents were calculated and drug-dependent factors were investigated as potential variables in determining the optimal scaling factor. The global exponents for scaling CM mAb PK data were 0.74 (CL), 0.80 (CL with Fc-modified mAbs excluded), 0.44 (CL with Fc-modified mAbs only), 0.71 (Q), 1.12 (V1), and 0.99 (V2). These values are in line with previously published literature values.

研发中单克隆抗体（monoclonal antibodies, mAbs）的复杂度不断提升，给从临床前数据预测人类药代动力学（pharmacokinetic, PK）参数带来了挑战。本分析旨在确定最优的异速缩放指数（allometric scaling exponents）。研究人员从公开文献中提取数据，构建了目前已公开的规模最大的中央数据库，收录了食蟹猴（cynomolgus monkey, CM）与人体中单克隆抗体的二室模型（two-compartment model）参数，样本量为59组（*n*=59）。研究人员计算了全局异速缩放指数，并将药物依赖性因素作为确定最优缩放因子的潜在变量进行了探究。用于食蟹猴单克隆抗体药代动力学数据缩放的全局指数如下：0.74（CL，总清除率，clearance, CL）、0.80（排除Fc修饰的单克隆抗体（Fc-modified mAbs）后的CL）、仅包含Fc修饰的单克隆抗体时的CL为0.44、0.71（Q，房室间转运速率常数，intercompartmental clearance, Q）、1.12（V1，中央室表观分布容积，apparent volume of distribution in central compartment, V1）以及0.99（V2，外周室表观分布容积，apparent volume of distribution in peripheral compartment, V2）。上述数值与已发表文献中的报道值一致。
研发中单克隆抗体（monoclonal antibodies, mAbs）的复杂度不断提升，给从临床前数据预测人类药代动力学（pharmacokinetic, PK）参数带来了挑战。本分析旨在确定最优的异速缩放指数（allometric scaling exponents）。研究人员从公开文献中提取数据，构建了目前已公开的规模最大的中央数据库，收录了食蟹猴（cynomolgus monkey, CM）与人体中单克隆抗体的二室模型（two-compartment model）参数，样本量为59组（*n*=59）。研究人员计算了全局异速缩放指数，并将药物依赖性因素作为确定最优缩放因子的潜在变量进行了探究。用于食蟹猴单克隆抗体药代动力学数据缩放的全局指数如下：0.74（CL，总清除率，clearance, CL）、0.80（排除Fc修饰的单克隆抗体（Fc-modified mAbs）后的CL）、仅包含Fc修饰的单克隆抗体时的CL为0.44、0.71（Q，房室间转运速率常数，intercompartmental clearance, Q）、1.12（V1，中央室表观分布容积，apparent volume of distribution in central compartment, V1）以及0.99（V2，外周室表观分布容积，apparent volume of distribution in peripheral compartment, V2）。上述数值与已发表文献中的报道值一致。