Advances in the application of physiologically-based pharmacokinetic model in EGFR-TKI precision therapy
- VernacularTitle:生理药代动力学模型在EGFR-TKI精准治疗中的应用进展
- Author:
Yingying YANG
1
,
2
;
Jiaqi SHAO
1
,
2
;
Qiulin XIANG
1
;
Guoxing LI
1
;
Xian YU
1
Author Information
1. Phase Ⅰ Clinical Trial Center，the Second Affiliated Hospital of Chongqing Medical University，Chongqing 400060，China
2. College of Pharmacy，Chongqing Medical University，Chongqing 400016，China
- Publication Type:Journal Article
- Keywords:
physiologically-based pharmacokinetic model;
EGFR-TKI;
precision treatment;
drug interaction;
non-small cell
- From:
China Pharmacy
2025;36(8):1013-1018
- CountryChina
- Language:Chinese
-
Abstract:
Epidermal growth factor receptor-tyrosine kinase inhibitor （EGFR-TKI） represent a class of small-molecule targeted therapeutics for oncology treatment， and serve as first-line therapy for advanced non-small cell lung cancer （NSCLC） with EGFR- sensitive mutations， with representative agents including gefitinib， dacomitinib， and osimertinib. In clinical practice， dose adjustment of EGFR-TKI may be required for cancer patients under special circumstances such as drug combinations or hepatic/ renal impairment. Physiologically-based pharmacokinetic （PBPK） model， capable of predicting pharmacokinetic （PK） processes in humans， has emerged as a vital tool for clinical dose optimization. This article sorts the modeling methodologies， workflows， and commonly used software tools for PBPK model， and summarizes the current applications of PBPK model in EGFR-TKI precision therapy as of June 30， 2024. Findings demonstrate that PBPK modeling methods commonly employ the “bottom-up” approach and the middle-out approach. The process typically involves four steps： parameter collection， compartment selection， model validation， and model application. Commonly used software for modeling includes Simcyp， GastroPlus， and open-source software such as PK- Sim. PBPK model can be utilized for predicting drug-drug interactions of EGFR-TKI co-administered with metabolic enzyme inducers or inhibitors， acid-suppressive drugs， or traditional Chinese and Western medicines. It can also adjust dosages in conjunction with genomics， predict PK processes in special populations （such as patients with liver or kidney dysfunction， pediatric patients）， evaluate the efficacy and safety of drugs， and extrapolate PK predictions from animal models to humans.
