单克隆抗体药代动力学药效学模型研究进展

治疗性单克隆抗体是目前新药研发的一个热点。和小分子药物相比，单克隆抗体药物相对分子质量大，与靶点的结合具有更高的特异性和选择性。用于描述其药代动力学(PK)和药效学(PD)行为的PK模型和PK/PD模型也有了新的发展。本文从吸收、分布、消除等方面综述了单克隆抗体药物的PK特征，对当前用于该类药物PK研究的靶点介导药物处置(TMDD)模型和生理药代动力学模型(PBPK)进行了介绍，并基于药物与靶点作用的4类应用(免疫毒性治疗、靶细胞消除、改变细胞功能和靶向给药)分别介绍了单克隆抗体药物的PK/PD模型。

Advances in pharmacokinetic and pharmacodynamic modeling of monoclonal antibody

The successes of therapeutic monoclonal antibodies(mAbs)in clinical practice has drawn more attention to mAbs development. Compared to chemical drugs with small molecules, mAbs have larger molecular weight; besides, they show much higher selectivity and specificity. As a result, new pharmacokinetic(PK)and pharmacokinetic/pharmacodynamic(PK/PD)models have been proposed to guide mAbs development. This article summarizes the unique PK characteristics of mAbs and introduces the models used in PK investigation of mAbs, such as target-mediated drug disposition(TMDD)model and physiologically based pharmacokinetic(PBPK)model. In addition, four different categories of PK/PD models for mAbs in immuno-toxicotherapy, target-cell elimination, alteration of cellular function and drug targeting are also reviewed in the present article.