Pharmacokinetic models compartment concept

Whereas classical pharmacokinetic models utilize a relatively small number of compartments (see Figure. 6.10), PBPK models seek to mimic physiological pathways and processes controlling the time-course of plasma and tissue concentrations and represent the state-of-the-art in advanced pharmacokinetic systems analysis. Basic concepts of PBPK modeling and a hybrid application to composite nanodevice pharmacokinetics are described in this section. 

Let us consider some drug administration practicalities. Up to now, the administered amounts were considered as initial units introduced simultaneously into several compartments at the beginning of the experiment. These amounts were considered as initial conditions to the differential equations describing the studied processes. Nevertheless, this concept seems to have limited applications in pharmacokinetics. In this section, we develop the probabilistic transfer and retention-time models associated with an extravascular or intravascular route of administration. 

Pharmacokinetics provides the scientific basis of dose selection, and the process of dose regimen design can be used to illustrate with a single-compartment model the basic concepts of apparent distribution volume (Vd), elimination half-life (b/2) and elimination clearance (CLg). A schematic diagram of this model is shown in Figure 2.4, along with the two primary pharmacokinetic parameters of distribution volume and elimination clearance that characterize it. 

In recent years, non-compartmental or model-independent approaches to pharmacokinetic data analysis have been increasingly utilized since this approach permits the analysis of data without the use of a specific compartment model. Consequently, sophisticated, and often complex, computational methods are not required. The statistical or non-compartmental concept was first reported by Yamaoka in a general manner and by Cutler with specific application to mean absorption time. Riegelman and Collier reviewed and clarified these concepts and applied statistical moment theory to the evaluation of in vivo absorption time. This concept has many additional significant applications in pharmacokinetic calculations. 

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