The peripheral compartment corresponds to organs for which the rate of equilibrium with blood is slower, the number of required peripheral compartments being indicated by the data itself. It is the reason why body clearance can be estimated by the product of K10 and Vc. The kidney and liver being the two most important clearing organs, drug elimination occurs from the central compartment (according to a first-order rate constant noted K10), and the volume of the central compartment (Vc) can be viewed as the apparent space from which drug elimination occurs. The central compartment corresponds to blood and all organs, which are in rapid equilibrium with blood (lungs, kidney and liver). The mammillary topography is due to the anatomy of the cardiovascular system, which irrigates different organs in a parallel pathway (rather than sequentially). The classical 2 or 3 compartmental mammillary models are a simplistic representation of the body in 2 or 3 well-stirred compartments. the physiological and anatomical reality (left). The figure shows the correspondence between a tricompartmental model (right) vs. By definition of volume of distribution (see Eqn 1): Considering that CT/ CP is equal to fu,P / fu,T: Total concentrations in plasma and tissue spaces are functions of the affinities of the drug in these spaces for the different components to which drug binds, and it is the free drug concentration which ‘controls’ the total drug concentration, not the reverse.Ĭompartmental model and the volume of distribution of the central compartment. According to the principle of mass balance, the total amount of drug in the body is equal to the amount in plasma (VPCP) plus the amount in tissue (VTCT). In extra-vascular space (volume VT), drug is also either free (open circle) or bound (black circle) to extra-vascular components when equilibrium is achieved, the unbound concentration (Cfree) in the vascular and extra-vascular spaces are the same and the free fraction in the extra-vascular space (fu,T) is the ratio Cfree/CT CT being the total concentration in extracellular space, i.e. Lower panel: only the free drug (open circle) can cross the capillary membrane and gain access to the extracellular fluids outside the plasma. The free fraction in plasma (fu,P) is the ratio Cfree/CP. The total concentration in plasma (CP) is the sum of bound (Cbound) and free (Cfree) concentrations. Upper panel: in plasma (volume: VP), drug is either free (open circle) or bound (black circle) to proteins or red blood cells. Principles of drug partition between vascular space (plasma) and non-vascular space (tissue), and establishment of a minimal model for volume of distribution.
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