Recent developments in physiologically based pharmacokinetic modeling

Abstract

Physiologically based pharmacokinetic (PBPK) modeling is a mechanism based mathematical modeling technique to predict and integrate drug absorption, distribution, metabolism and excretion (ADME) of a compound in animals and human. A PBPK model maps the transfer of drug through different "organ" compartments and accounts for anatomical, physiological, physical, and chemical properties that influence ADME processes. Thus, application of PBPK has been of great interest lately in various phases of drug discovery and development. However, until recently PBPK based approaches could not be frequently applied within pharmaceutical industry because of the complexity of the model and the difficulty in obtaining necessary input parameters for a PBPK model, such as labor intensive tissue-toplasma partition coefficient. In recent years, further improvement of in vitro, ex vivo, and in silico methods to provide input variable information has significantly increased the applicability of the PBPK based approach. In addition, several software programs have incorporated relevant PBPK equations and have made its application more widespread and simpler. More recently, the support of regulatory agencies for use of PBPK based methods has also encouraged drug developers to apply this technique in drug development. This chapter describes whole-body PBPK modeling methodology and its various applications in pharmaceutical industry. © American Association of Pharmaceutical Scientists 2011.