大分子药物的吸收、分布、代谢、排泄和毒性特征及药代模型的应用

Absorption, distribution, metabolism, excretion and toxicity of biologics and its application in pharmacokinetic modeling

摘要: 近年来，大分子药物受到越来越多的关注，如单克隆抗体等，已成为21世纪药物研发中最具发展前景的领域之一。由于结构的差异，与小分子药物相比，大分子药物在体内具有不同的吸收（absorption）、分布（distribution）、代谢（metabolism）、排泄（excretion）及毒性（toxicity）过程（ADMET），这导致大分子药物具有与小分子药物不同的药代特征，药代模型在大分子药物的研发和临床应用中也发挥着越来越重要的作用。对于大分子药物的药代动力学特征和模型拟合，须具体药物具体分析，本文就大分子的ADMET特征以及在PK模型中的应用展开综述。

Abstract: Recently, more and more attentions of drug development are placed to macromolecules, such as monoclonal antibodies, proteins, etc. It has become one of the most promising areas in drug research and development in 21st Century. In terms of the structure and the ADMET (absorption, distribution, metabolism, excretion and toxicity), macromolecules is different from small molecule drugs, which lead to a distinct modeling strategy. The characterization of biologics ADMET processes and its application in the PK model selection of macromolecules are reviewed in this paper.