靶点介导的药物处置模型在单克隆抗体药物研发中应用的探讨

近年来，国内外诸多企业正在积极地进行单克隆抗体药物的研发和申报。作为一种大分子蛋白药物，单克隆抗体因其特殊的结构和生理性质，在体内的吸收、分布、代谢及排泄与小分子药物相比均存在较大差异。单抗具有的靶点介导的药物处置、非线性药动-代谢、时间依赖性、较长的半衰期等独特的药代动力学特征，使得其在药物研发过程中存在了一系列的挑战。合理的应用模型和仿真技术可帮助研究者充分发掘数据信息、预测临床试验结果、指导临床试验设计以及优化给药方案等，其中靶点介导的药物处置模型在单抗药物研发中的应用目前已有一些探索。本文将通过对单抗药物药动学特征的介绍，探讨靶点介导的药物处置模型在单抗药物研发中应用的可行性和必要性，以期帮助研究者科学、高效地进行单抗类药物的研发。

Application of target-mediated drug disposition (TMDD) models in the development of monoclonal antibody

In recent years, monoclonal antibodies have become the area of interest in industry. Unlike small molecules, monoclonal antibodies exhibit unique structural and physiological properties, alongside with differences in absorption, distribution, metabolism and excretion. These unique properties of monoclonal antibodies［e.g. target-mediated drug disposition (TMDD), nonlinear pharmacokinetics, time-dependence and long half-life］ pose several challenges in drug development. Appropriate application of modeling and simulation techniques can help researchers with data mining, predicting clinical trial outcomes, guiding clinical trial designs and optimizing dosing schemes. Among these, the application of the TMDD model in the monoclonal antibody development is growing. In this review, a brief introduction on the pharmacokinetic properties of monoclonal antibodies is provided, followed by a discussion on the feasibility and necessity of applying the TMDD model to monoclonal antibody drug development. The aim of current work is to provide a reference for researchers to scientifically and efficiently conduct studies on the monoclonal antibodies.