An engineering oriented approach to physiologically based pharmacokinetic and pharmacodynamic modeling

Pharmaceutical industry and regulatory agencies consider mathematical modeling as a valuable tool to increase the productivity of pharmaceutical research and the efficiency of new drug development processes. This chapter provides an engineering-oriented approach to the definition of pharmacokinetic and pharmacodynamic models with the target of covering and meeting the directives of quantitative systems pharmacology. In particular, we extensively discuss the use of physiologically based pharmacokinetic models and the coupling with alternative versions of pharmacodynamic models. Model designs and the derived equations are critically engaged with a multidisciplinary perspective to acknowledge both anatomical/physiological consistency and mathematical correctness, including model-identifiability issues and parameters-uncertainty assessment. The purpose is to provide a general framework for engineers and pharmaceutical scientists approaching this discipline.