Fractal volume of drug distribution: It scales proportionally to body mass

Purpose, To develop the physiologically sound concept of fractal volume of drug distribution, nu (f) and evaluate its utility and applicability in int erspecies pharmacokinetic scaling. Methods, Estimates for nu (f) of various drugs in different species were ob tained from the relationship: nu (f) = (nu - V-pl) V-ap-V-pl/V-ap + Vpl where nu is the total volume of the species (equivalent to its total mass a ssuming a uniform density 1g/mL), V-pl is the plasma volume of the species and V-ap is the conventional volume of drug distribution. This equation was also used to calculate the fractal analogs of various volume terms of drug distribution (the volume of central compartment, V-c. the steady state vol ume of distribution, V-ss, and the volume of distribution following pseudod istribution equilibrium, V-z). The calculated fractal volumes of drug distr ibution were correlated with body mass of different mammalian species and a llometric exponents and coefficients were determined. Results, The calculated values of nu (f) for selected drugs in humans provi ded meaningful and physiologically sound estimates for the distribution of drugs in the human body. For all fractal volume terms utilized, the allomet ric exponents were found to be either one or close to unity. The estimates of the allometric coefficients were found to be in the interval (0,1). Thes e decimal values correspond to a fixed fraction of the fractal volume term relative to body mass in each one of the species. Conclusions. Fractal volumes of drug distribution scale proportionally to m ass. This confirms the theoretically expected relationship between volume a nd mass in mammalian species.