Foundations of pharmacodynamic systems analysis

The pillars of pharmacodynamic modeling are the pharmacokinetics of the drug, the nature of the pharmacology that underlies drug interactions with their targets, and the physiology of the system considering molecular to whole body levels of organization and functioning. This chapter provides a general assessment of the fundamental components and some interactions of each of these pillars indicating how they serve as building blocks for systems models. Key elements of pharmacokinetics include the operation of Fick’s Laws for diffusion and perfusion along with the often nonlinear mechanisms of drug distribution and elimination. Target-binding relationships in pharmacology evolve from the law of mass action producing capacity-limitation in most operative control functions. Mammalian physiology and pathophysiology feature a wide breadth of turnover rates for biological compounds, structures, and functions ranging from rapid electrical signals to lengthy human lifespans, which often determine the rate-limiting process and basic type of model to be applied. Appreciation of the diverse array, mechanisms, and interactions of individual components that comprise the pillars of pharmacodynamics can serve as the foundation for building more complex systems models.