Development and application progress of physiologically based pharmacokinetic modeling and its combined use with other modeling methods / 中国临床药理学与治疗学

ABSTRACT

Physiologically based pharmacokinetics (PBPK) is one of the main research fields of pharmacometrics, and it plays an important role at all the stages of drug development and clinical practice. In early drug discovery and development, human pharmacokinetics (PK) could be predicted by PBPK modeling using in silico, in vitro and preclinical in vivo data. During clinical studies, PBPK model could be used to investigate the effects of various physiological and pathological factors on PK, such as age, gender, liver/kidney impairment, and to guide dose adjustment of special population (pregnant women, children, etc.). Furthermore, PBPK modeling is now becoming more appealing with the ability to predict drug-drug interaction (DDI) in the case of co-administration of multiple drugs. In recent years, the application of PBPK modeling in industry has increased widely. Also, regulatory agencies have recognized the potential of PBPK and its impact on labeling recommendations. As the popularity of model-informed drug development, the combination of PBPK modeling with other commonly used modeling methods, such as population pharmacokinetics (PopPK), pharmacokinetic/pharmacodynamic (PK/PD) modeling and model-based meta-analysis (MBMA), has shown attractive advantages. In this paper, the origin and development, as well as the application status of PBPK are introduced briefly, and the application of PBPK modeling merged with PopPK, PK/PD and MBMA is reviewed.