Compartmental models, definition

Until now, the compartmental model was considered as consisting of compartments associated with several anatomical locations in the living system. The general definition of the compartment allows us to associate in the same location a different chemical form of the original molecule administered in the process. In other words, the compartmental analysis can include not only diffusion phenomena but also chemical reaction kinetics. 

From previous chapters it is clear that the evaluation. of pharmacokinetic parameters is an essential part of understanding how drugs function in the body. To estimate these parameters studies are undertaken in which transient data are collected. These studies can be conducted in animals at the preclinical level, through all stages of clinical trials, and can be data rich or sparse. No matter what the situation, there must be some common means by which to communicate the results of the experiments. Pharmacokinetic parameters serve this purpose. Thus, in the field of pharmacokinetics, the definitions and formulas for the parameters must be agreed upon, and the methods used to calculate them understood. This understanding includes assumptions and domains of validity, for the utility of the parameter values depends upon them. This chapter focuses on the assumptions and domains of validity for the two commonly used methods — noncompartmental and compartmental analysis. Compartmental models have been presented in earlier chapters. This chapter expands upon this, and presents a comparison of the two methods. 

The pharmacokinetic parameters descriptive of the system are as follows (although these definitions apply to both noncompartmental and compartmental models, some modification will be needed for two accessible pool models as well as compartmental models) ... 

The LSA linear drug disposition definition does not impose any restrictions on the mathematical form of the drug input response. This is in contrast to linear compartmental models. For example, a two-compartment model implies a biexponential response to an IV bolus injection ... 

Let us start with some definitions. A compartment is an amount of material that acts as though it is well-mixed and kinetically homogeneous. A compartmental model consists of a finite number of compartments with specified interconnections among them. The interconnections represent fluxes of material which physiologically represent transport from one location to another or a chemical transformation, or both, or control signals. An example of a simple two-compartment model is Ulustrated in Figure 9.1 where the compartments are represented by circles and the interconnections by arrows. 

This definition remains model-dependent, but VDSS can be calculated using a non-compartmental approach, which does not require any assumptions about the pharmacokinetic model concerned (see below). 

Gompartmental models have been the foundation of pharmacokinetic data analysis. The compartmental approach is presented here to facilitate definition of important pharmacokinetic parameters. Gompartmental models are determin-... 

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