The combined application of PBPK model and PopPK model in the dose selection of pediatric drug development: an example of rivaroxaban
10.16438/j.0513-4870.2022-0880
- VernacularTitle:联合应用PBPK模型和PopPK模型助力儿科用药研发中的剂量选择: 以利伐沙班为例
- Author:
Wei-zhe JIAN
;
Rong CHEN
;
Tian-yan ZHOU
- Publication Type:Research Article
- Keywords:
model-informed drug development;
pediatric drug;
population pharmacokinetic model;
physiologically based pharmacokinetic model;
rivaroxaban
- From:
Acta Pharmaceutica Sinica
2022;57(10):3157-3162
- CountryChina
- Language:Chinese
-
Abstract:
Model-informed drug development (MIDD) in the development of pediatric drugs is drawing more and more attention due to the insufficiency of subjects, lack of research on ontogeny, and the limitation of ethic. The core of MIDD used for dose selection includes the population pharmacokinetic (PopPK) model and physiologically based pharmacokinetic (PBPK) model, as well as model-based simulation and prediction. PBPK model has the advantage of predicting the optimal pediatric dose before the clinical trials and has the ability of extrapolation from adult model to pediatric model. PopPK model characterizes the pediatric PK feature based on the analysis of clinical data and can be used to explore the significant covariates, which is a power tool for individualized medicine in children. With their own advantages and disadvantages, PBPK and PopPK model should be jointly used in the pediatric drug development to refine the dose regimen for children at different ages. In this study, the pediatric drug development of rivaroxaban was taken as an example to introduce the combined application of PBPK model and PopPK model in the design and validation of pediatric dose regimen in Phase Ⅰ, Ⅱ and Ⅲ trials, which may provide reference to MIDD in other pediatric drug development.
