Simon Peter Rowland, Emma Nixon, Krithika Mohan, Qianwen Wang, James W T Yates
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引用次数: 0
摘要
开发中的 mAbs 越来越复杂，给从临床前数据预测人体药代动力学（PK）参数带来了挑战。我们从文献中提取数据，创建了一个中央数据库（目前最大的已发表数据库），其中包含了犬科猴（CM）和人类 mAbs（n = 59）的两室模型参数。计算了全局异速指数，并研究了药物依赖因素作为确定最佳缩放因子的潜在变量。缩放 CM mAb PK 数据的全局指数分别为 0.74（CL）、0.80（CL 不包括 Fc 修饰的 mAb）、0.44（CL 仅包括 Fc 修饰的 mAb）、0.71（Q）、1.12（V1）和 0.99（V2）。这些数值与之前发表的文献数值一致。
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 (n = 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.
期刊介绍：
Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology
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