The purpose of this review was to assess the advancement of applications for physiologically based pharmacokinetic (PBPK) modeling in various therapeutic areas. We conducted a PubMed search, and 166 articles published between 2012 and 2018 on FDA-approved drug products were selected for further review. Qualifying publications were summarized according to therapeutic area, medication(s) studied, pharmacokinetic model type utilized, simulator program used, and the applications of that modeling. The results showed a 13-fold increase in the number of papers published from 2012 to 2018, with the largest proportion of articles dedicated to the areas of infectious diseases, oncology, and neurology, and application extensions including prediction of drug-drug interactions due to metabolism and/or transporter-mediated effects and understanding drug kinetics in special populations. In addition, we profiled several high-impact studies whose results were used to guide package insert information and formulate dose recommendations. These results show that while utilization of PBPK modeling has drastically increased over the past several years, regulatory support, lack of easy-to-use systems for clinicians, and challenges with model validation remain major challenges for the widespread adoption of this practice in institutional and ambulatory settings. However, PBPK modeling will continue to be a useful tool in the future to assess therapeutic drug monitoring and the growing field of personalized medicine.Keywords Physiologically based pharmacokinetic modeling . PBPK modeling applications . Modeling and simulation . In vitro in vivo extrapolation . Personalized medicine
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