Physiological models

An alternate method of building a pharmacokinetic profile of a drug in the body is to utilize anatomic and physiological information. Such a model does not make assumptions about body compartments or first order processes for drug absorption and elimination.16 The first step in such modelling is to decide whether drug distribution into a particular tissue is perfusion rate or membrane transport limited.2 These decisions are based on the physicochemical characteristics of the drug and physiological conditions in addition to reference to any experimental data. In order to write a mass balance equation, blood flow, Q, and the volume, V, of the organ or tissue of interest is needed and may be obtained frrom the literature. The other parameters, venous drug concentration, Cv, and the partition coefficient, R, are determined experimentally.2 A simple mass balance equation may be written as:2

where t = tissue.

Mass balance equations may be constructed for each organ or tissue considered and algebraic equations added to account for growth, changes in tissue weight ratios, and other physiological parameters.The advantage of this modelling over the more traditional compart-mental method is provision of a time course of drug distribution to any organ or tissue, and this model allows estimation of the effects of changing physiological parameters on tissue concentrations. Disadvantages include the need for complex mathematical equations and the lack of data on the physiological parameters necessary to construct the differential equations.2

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