Pharmacokinetic and Toxicokinetic Models

Structural Models

traditionally, the structural component of pk/TK models have been described by a system of ordinary differential equations (ode) that describe the time course of the concentration of the compound(s) of interest in the body. the level of complexity of these equations will depend on many factors, but in general they seek to relate the changes in the observed concentrations with time (output) as a function of how the compound was administered (input) and how the body handled it (disposition). this disposition component is perhaps the one that imparts the most complexity in the structural model. on one hand, the modeler could assume that the compound is distributed through different organs at different transfer rates. on the other hand, the modeler can simply assume that body in general is a collection of compartments, not necessarily physiologically based, where the amount of material acts kinetically like a distinct, homogeneous, well-mixed amount of the material.8 While it may seem appealing at first to model the disposition of a drug using a physiological basis, the mathematical complexity is reduced considerably by using compartmental modeling instead, and for this reason, compartmental models are the mainstay of pk/TK modeling.

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