《基于药代动力学方法支持PD-1/PD-L1单抗治疗肿瘤患者的替代剂量方案选择指南》解读  

Interpretation of pharmacokinetic-based criteria for supporting alternative dosing regimens of programmed cell death receptor-1(PD-1) or pro-grammed cell death-ligand 1(PD-L1) blocking antibodies for treatment of patients with cancer guidance for industry

作　　者：刘维[1] 薛钧升 于之恒 王紫愉 陈镕[2] 周田彦[2] LIU Wei;XUE Junsheng;YU Zhiheng;WANG Ziyu;CHEN Rong;ZHOU Tianyan(Peking University Third Hospital,Department of Pharmacy,Beijing 100191,China;Department of Pharmaceutics,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China;Peking University Third Hospital,Department of Obstetrics and Gynecology,Beijing 100191,China)

机构地区：[1]北京大学第三医院药剂科,北京100191 [2]北京大学药学院药剂学系,北京100191 [3]北京大学第三医院妇产科,北京100191

出　　处：《中国临床药理学与治疗学》2022年第1期86-94,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金面上项目(82073919)。

摘　　要：近年来,以定量药理学为基础的模型化与仿真技术在新药研发中的地位日益凸显。2021年8月,FDA发布了《基于药代动力学方法支持PD-1/PD-L1单抗治疗肿瘤患者的替代剂量方案选择指南》征求意见稿(以下简称"《指南》"),提出基于群体PK(Pop-PK)模型仿真寻找替代方案的必要性和具体实施标准。本文首先对PD-1/PD-L1单抗的现有临床方案以及该指南的内容进行了总结,随后列举了基于Pop-PK仿真方法辅助替代方案获批的既往实际案例,并进一步分析了该指南用于PD-1/PD-L1单抗替代方案优化的要点,展望其对PD-1/PD-L1单抗临床研发的意义和价值,以期为国内同行提供参考。In recent years, modeling and simulation technology based on pharmacometrics has received increasing attention in the development of innovation drugs. In August of 2021, FDA issued a guidance named Pharmacokinetic-Based Criteria for Supporting Alternative Dosing Regimens of Programmed Cell Death Receptor-1(PD-1) or Programmed Cell Death-Ligand 1(PD-L1) Blocking Antibodies for Treatment of Patients with Cancer Guidance for Industry, claiming the necessity of using population PK-based simulation method for the optimization of dosing regimens, and the corresponding implementation standards. This article first summarized the existing therapeutic regimens of PD-1/PD-L1 blocking antibodies in clinic as well as the main content of the guidance, and then cited some actual examples where population PK-based simulation method did contribute to the approval of the alternative dosing regimens. Besides, some critical considerations for the dosing regimen optimization of PD-1/PD-L1 blocking antibodies were also analyzed. In our view, this guidance would have positive impacts on the development of PD-1/PD-L1 blocking antibodies in the future. We hope that this article may provide some references for the colleagues in China.

关 键 词：定量药理学 群体PK 模型仿真 模型引导的药物研发 

分 类 号：R969[医药卫生—药理学]