%0 Journal Article %A Jennifer E Sager %A Jinngjing Yu %A Isabelle Raguenau-Majlessi %A Nina Isoherranen %T Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A systematic review of published models, applications and model verification %D 2015 %R 10.1124/dmd.115.065920 %J Drug Metabolism and Disposition %P dmd.115.065920 %X Modeling and simulation of drug disposition has emerged as an important tool in drug development, clinical study design and regulatory review, and the number of physiologically based pharmacokinetic (PBPK) modeling related publications and regulatory submissions have risen dramatically in recent years. However, the extent of use of PBPK modeling by researchers, and the public availability of models has not been systematically evaluated. This review evaluated PBPK-related publications to 1) identify the common applications of PBPK modeling, 2) determine ways in which models are developed, 3) establish how model quality is assessed and 4) provide a list of publically available PBPK models for sensitive P450 and transporter substrates as well as selective inhibitors and inducers. PubMed searches were conducted using the terms PBPK and physiologically based pharmacokinetic model to collect published models. Only papers on PBPK modeling of pharmaceutical agents in humans published in English between 2008 and May 2015 were reviewed. A total of 366 PBPK-related articles met the search criteria with the number of articles published per year rising steadily. Published models were most commonly used for drug-drug interaction (DDI) predictions (28%), followed by interindividual variability and general clinical pharmacokinetic predictions (23%), formulation or absorption modeling (12%) and predicting age related changes in pharmacokinetics and disposition (10%). 106 models of sensitive substrates, inhibitors and inducers were identified. An in-depth analysis of the model development and verification revealed a lack of consistency in model development and quality assessment practices demonstrating a need for development of best-practice guidelines. %U https://dmd.aspetjournals.org/content/dmd/early/2015/08/21/dmd.115.065920.full.pdf