Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Int Immunopharmacol. 2021 Aug;97:107703. doi: 10.1016/j.intimp.2021.107703. Epub 2021 Apr 30.
Immune checkpoint inhibitors (ICIs) have been demonstrated an effective treatment in multiple tumor type, which restore the immune response to against cancer cell. Currently, approved ICIs include anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4); anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) monoclonal antibodies (mAbs). In most these drugs, unique pharmacokinetic (PK) and pharmacodynamics (PD) have shown significant influence on clinical outcomes, which occurred by target-mediated drug concentration and time-varying drug clearance. An exposure-response (E-R) relationship has been used to describe the safety and efficacy of ICIs, and shown a plateaued E-R and time dependent changes in exposure. Using an enzyme linked immunosorbent assay (ELISA) or LC-MS/MS method to measure the peak concentration, trough concentration or area under the curve (AUC) of ICIs to assess the drug exposure. There are lots of covariates that have an influence on exposure, such as sex, clearance, body weight and tumor burden. In this review, we pooled data from studies of concentration or other pharmacokinetics parameter of mAbs to assess E-R in efficacy and safety.
免疫检查点抑制剂 (ICIs) 在多种肿瘤类型中已被证明是一种有效的治疗方法，它可以恢复机体对癌细胞的免疫反应。目前，已批准的 ICI 包括抗细胞毒性 T 淋巴细胞抗原 4（CTLA-4）；抗程序性细胞死亡蛋白 1（PD-1）和抗程序性细胞死亡配体 1（PD-L1）单克隆抗体（mAbs）。在这些药物中，独特的药代动力学（PK）和药效动力学（PD）对临床结局有显著影响，这是通过靶介导的药物浓度和时变药物清除率发生的。暴露-反应（E-R）关系已被用于描述 ICI 的安全性和疗效，并显示出 E-R 的平台化和暴露的时间依赖性变化。使用酶联免疫吸附测定（ELISA）或 LC-MS/MS 方法来测量 ICI 的峰浓度、谷浓度或曲线下面积（AUC），以评估药物暴露情况。有许多协变量会影响暴露，如性别、清除率、体重和肿瘤负担。在这篇综述中，我们汇集了来自浓度或其他药代动力学参数研究的数据，以评估疗效和安全性中的 E-R。
