Pharmacokinetic/pharmacodynamic models of anti-tumor agents in xenograft mice: historical review, recent advances, and application in drug development
10.16438/j.0513-4870.2020-1121
- VernacularTitle:基于异植瘤小鼠的抗肿瘤药PK/PD模型: 历史回顾、研究进展与应用实践
- Author:
Kuan HU
;
Kai HUA
;
Jin YANG
- Publication Type:Research Article
- Keywords:
anti-cancer therapy;
PK/PD model;
combinatorial therapy;
xenograft mice;
quantitative pharmacology
- From:
Acta Pharmaceutica Sinica
2020;55(11):2580-2594
- CountryChina
- Language:Chinese
-
Abstract:
Xenograft mice are preclinical animal models of tumors and are widely utilized in anti-tumor research. PK/PD modeling of anti-tumor agents is an approach that can capture the time profile of the "dose-plasma concentration-biomarker level-tumor volume" process based on experimental data from xenograft mice using a non-linear mixed-effect model. PK/PD modeling can help optimize the dosing regimen for anti-tumor therapy, evaluate any synergistic effect and help identify an optimal schedule for combination therapy, as well as providing a preliminary estimate of a drug's efficacy and anti-tumor potency in the human body. PK/PD modeling can also help by quantitatively explaining the mechanism of the tumor-inhibitory effect as indicated by changes in biomarker levels after a drug acts on its target. This article provides a systematic summary of the background, application range, and limitations of the mainstream anti-tumor agent PK/PD models. Recent advances in model structure development are reviewed in detail. Finally, we discuss promising applications of PK/PD models in anti-tumor medicine development from the perspective of a drug's mechanism of action, optimization of combination therapy schedules, and their clinical translation.
