Whole-body physiologically based pharmacokinetic models.

This review summarizes the most recent developments in and applications of physiologically based pharmacokinetic (PBPK) modeling methodology originating from both the pharmaceutical and environmental toxicology areas. It focuses on works published in the last 5 years, although older seminal papers have also been referenced. After a brief introduction to the field and several essential definitions, the main body of the text is structured to follow the major steps of a typical PBPK modeling exercise. Various applications of the methodology are briefly described. The major future trends and perspectives are outlined. The main conclusion from the review of the available literature is that PBPK modeling, despite its obvious potential and recent incremental developments, has not taken the place it deserves, especially in pharmaceutical and drug development sciences.