Significance of ratios of different volumes of distribution in pharmacokinetics.

Multicompartmental pharmacokinetics involves the four volumes: Vc = volume of the central compartment; Vss = volume of distribution steady-state; V beta = volume of distribution beta; and Vext = the extrapolated volume of distribution. The ratio Vc/Vext is indicative of the degree of multicompartmental character of a set of data. The quantity (Vext/V beta)--1 is the fractional error in the total clearance when one assumes a monoexponential rather than a polyexponential equation for disposition of a drug. The ratio Vss/V beta indicates how well the one-compartment body model predicts average amounts of drug in the body when a multicompartmental model is actually operative. The quantity (Vss/Vc)--1 is equal to either k12/k21 or k12/k21 + k13/k31 of the two- and three-compartmental mammillary models. Examples from the literature are reported and discussed.