Shifting Focus from Fundamentals to Systems Pharmacodynamic Models

Abstract

Several mechanistic pharmacokinetic-pharmacodynamic (PK/PD) models have developed,
expanding upon several traditional pharmacology foundations, and are based on
pharmacological action mechanisms and main physiological rate-limiting or turnover
processes. Tolerance is only one of several complexity that may be added to a variety of
basic models, which can then be used as building blocks to construct improved PK/PD or
small system models. All of these ideas, together with aspects of both the vertical and
horizontal integration of molecular to whole-body processes, are shown in our
corticosteroid models. We outline the possible benefits and drawbacks of shifting PK/PD
toward systems models.