生理药代动力学模型及其在健康风险评价中的应用研究进展

Research advances of the physiologically based pharmacokinetic(PBPK) models and their applications in health risk assessment

生理药代动力学(Physiologically Based Pharmacokinetic,PBPK)模型在健康风险评估中的应用逐渐成为研究的焦点。简要阐述了PBPK模型的定义及发展历程,在此基础上详细介绍了PBPK模型建立的过程及其在致癌风险评估、混合物健康风险评估中的应用。最后,总结了该模型在健康风险评估应用中的受限因素,提出跨学科合作有利于解决这些受限因素,从而进一步推进该模型在混合物健康风险评价中的应用。

The present paper is inclined to bring about a research review on the advances in making the physiologically based pharmacokinetic（PBPK） models and their applications to the health risk assessment.As is known,the PBPK models are very important and useful mathematical models based on the physiology,biochemistry,and anatomy of the organisms.Such models tend to adopt the algebraic and differential equations for describing the uptake,distribution,metabolism,and excretion of chemicals according to the law of mass conservation and,for such models help to reduce the uncertainty but increase the accuracy of the health risk assessment.And it is for the above reasons that the science giants in the line have won more attention to the law from the researchers to further develop such models in recent years.However,most of such models have still had their own respective limits,which prevent them from being more widely applied at least in the health risk assessment.In this paper,we would like to make a summary of the detailed modeling process of PBPK,their applications and their confining factors.And we wish to promote more popular application of the PBPK models in the risk assessment.Firstly,we have briefly introduced the definition and research status of PBPK models.Secondly,what we can do is to introduce mainly the detailed modeling process of the models,including the model structure,mathematical equations,the model-building parameters,the solutions to the PBPK modeling equations and validation/calibration.What is more,we have also displayed how to use them in the carcinogenic risk detection and those with the chemical mixtures in this paper.The applications of such models to the carcinogenic risk may include the extrapolation and variability of the interspecies,the routeto-route extrapolation,high-to-low-dose extrapolation,etc.Moreover,we have also provided samples on how to illustrate the application methods.And,finally,it is necessary to point out the application limits of the PBPK models in health risk assessment.Starting from the current research situations,the confining factors mainly include the complex modeling proeess,lack of relevant experimental data,difficulties in the mixed modeling,lack of heavy metal modes,lack of simplified solutions and so on.Therefore,close cooperation and coordination are called for to solve the aforementioned problems through joined efforts so as to promote further applications of the PBPK models to the risk assessment area.