生物大分子药物代谢消除途径及体外代谢研究方法进展

Advances in in Vitro Research Methods for The Metabolism of Bio-macromolecular Drugs

由于理化及生物学性质的差异,生物大分子药物与传统小分子药物相比,药代动力学机制更加复杂,在体内表现出不同的吸收、分布、代谢、排泄过程。大分子药物一般不经CYP 450酶代谢,其体内消除途径主要有肾小球滤过、酶水解、受体介导的胞吞消除和抗药物抗体介导的消除。近年来,除了常用的免疫分析法、放射性同位素示踪法、LC-MS/MS等分析方法外,还有计算机模型被开发用于模拟预测大分子药物药代动力学性质的研究并发挥越加重要的作用。本文主要综述了大分子药物主要代谢消除途径及体外研究模型TMDD、PBPK的应用和发展。

Compared with conventional small molecule drugs,biomacromolecule drugs have more complex pharmacokinetic mechanisms and exhibit unique processes of absorption,distribution,metabolism and excretion in vivo due to their different physicochemical and biological properties.Generally,macromolecular drugs are not metabolized by CYP enzymes.Their main elimination pathways include glomerular filtration,enzymatic hydrolysis,receptor-mediated endocytosis and anti-drug antibodymediated elimination.In addition to immunoassay methods,radioisotope tracer methods and LC-MS/MS analysis methods,computer models have also been developed to simulate and predict the pharmacokinetic properties of macromolecular drugs in recent years.This article mainly reviews the main metabolic pathway of macromolecular drugs and the application and development of the in vitro prediction models.