Significance of ratios of different volumes of distribution in pharmacokinetics

Multicompartmental pharmacokinetics involves the four volumes: V_c = volume of the central compartment; V_ss = volume of distribution steady-state; V_β = volume of distribution beta; and V_ext = the extrapolated volume of distribution. The ratio V_c/V_ext is indicative of the degree of multicompartmental character of a set of data. The quantity (V_ext/V_β)?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 V_ss/V_β 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 (V_ss/V_c)? 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.