儿童生理药代动力学模型及其建模软件的应用  

Physiological pharmacokinetic model of children and its application of modeling software

作　　者：周旭 魏园园 马涛 唐跃洲 党云洁[1] 曹德英[1] ZHOU Xu;WEI Yuan-yuan;MA Tao;TANG Yue-zhou;DANG Yun-jie;CAO De-ying(School of Pharmacy,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学药学院,河北石家庄050017

出　　处：《药学学报》2023年第2期320-329,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金项目(81973251);河北省自然科学基金项目(H2020206610);河北省2022引进留学人员资助项目(C20220345);河北医科大学2022年大学生创新性实验计划项目(USIP2022225).

摘　　要：儿童的发育变化会影响药物的处置和临床效果,基于生理的药代动力学(physiologically-based pharmacokinetics,PBPK)模型是一种数学模型,可用于预测儿童的血药浓度,并深入了解年龄依赖性生理差异对药物处置的影响。儿童PBPK(pediatric PBPK,P-PBPK)模型在过去十年中引起了人们的关注,在学术界、制药公司和监管机构的共同努力下,现在已经有了越来越多用PBPK模型进行儿童临床研究的例子,尽管如此,P-PBPK模型的数量及其预测性能仍然落后于成人模型。笔者通过查阅文献,总结了药物在儿童和成人体内不同的吸收、分布、代谢和排泄(ADME)过程,分析了P-PBPK模型建立的一般原则,总结了常用的P-PBPK建模软件的功能和应用实例,以期为建模软件在P-PBPK中的合理应用提供依据。Developmental changes in children can affect drug disposition and clinical effects.A physiologicallybased pharmacokinetic(PBPK)model is a mathematical model that can be used to predict blood drug concentrations in children and gain insight into age-dependent physiological differences in drug disposition impact.Pediatric PBPK(P-PBPK)models have attracted attention over the past decade.With the concerted efforts of academia,pharmaceutical companies,and regulatory agencies,there are more and more examples of pediatric clinical studies using PBPK models.Nevertheless,the number of P-PBPK models and their predictive performance still lag behind adult models.By referring to the literature,we study the process of children adapting to adult absorption,distribution,metabolism,and excretion(ADME)parameters and analyze the general principles of P-PBPK model establishment.In addition,we summarize the functions and application examples of commonly used P-PBPK modeling software to provide a basis for the rational application of modeling software.

关 键 词：药物处置 预测 基于生理的药代动力学模型 儿童生理药代动力学模型 建模软件 

分 类 号：R945[医药卫生—微生物与生化药学]