Recent Progress on Physiologically Based Pharmacokinetic (PBPK) Model: A Review Based on Bibliometrics

Physiologically based pharmacokinetic/toxicokinetic (PBPK/PBTK) models are designed to elucidate the mechanism of chemical compound action in organisms based on the physiological, biochemical, anatomical, and thermodynamic properties of organisms. After nearly a century of research and practice, good results have been achieved in the fields of medicine, environmental science, and ecology. However, there is currently a lack of a more systematic review of progress in the main research directions of PBPK models, especially a more comprehensive understanding of the application in aquatic environmental research. In this review, a total of 3974 articles related to PBPK models from 1996 to 24 March 2024 were collected. Then, the main research areas of the PBPK model were categorized based on the keyword co-occurrence maps and cluster maps obtained by CiteSpace. The results showed that research related to medicine is the main application area of PBPK. Four major research directions included in the medical field were "drug assessment", "cross-species prediction", "drug-drug interactions", and "pediatrics and pregnancy drug development", in which "drug assessment" accounted for 55% of the total publication volume. In addition, bibliometric analyses indicated a rapid growth trend in the application in the field of environmental research, especially in predicting the residual levels in organisms and revealing the relationship between internal and external exposure. Despite facing the limitation of insufficient species-specific parameters, the PBPK model is still an effective tool for improving the understanding of chemical-biological effectiveness and will provide a theoretical basis for accurately assessing potential risks to ecosystems and human health. The combination with the quantitative structure-activity relationship model, Bayesian method, and machine learning technology are potential solutions to the previous research gaps.