Physiological pharmacokinetic models: some aspects of theory, practice and potential

Models are intellectual constructs that pattern selected relationships among the elements of one system to correspond in some way to elements of a second system. In pharmacokinetics, physiological models provide a clearly articulated, rational, explanatory basis for the integration of empirical data; they do this by partitioning the biological system into relevant components (tissues, organs, etc.) and linking them together through the circulatory system. Unlike conventional mammillary compartment models, there is a clear correspondence between model system elements and physiological entities. By virtue of their high degree of physical and biochemical relevance, these models can help provide deep insight into structure, function and mechanism. Pharmacokinetic (and potentially pharmacodynamic) response-time relationships can thus be understood in terms of interconnections and behavior of constituent subsystems. At their worst, these models provide stale or infertile views of reality and thus frustrate and alienate us with the triviality of their insights. At their best, they allow us to understand the accumulation of thought in pharmacokinetics and pharmacodynamics, and help with the integration of data and improvement of experimental design.