Pharmacokinetic/pharmacodynamic models of anti-tumor agents in xenograft mice: historical review, recent advances, and application in drug development / 药学学报
Acta Pharmaceutica Sinica
;
(12): 2580-2594, 2020.
Article
in Chinese
| WPRIM
| ID: wpr-837527
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Type of study:
Prognostic study
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2020
Type:
Article
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