Pharmacokinetic parameters for interspecies scaling using allometric techniques

Abstract

Pharmacokinetic models characterize the kinetic behavior of natural and synthetic substances in animals and man. While the same model structure can generally be used for a particular substance in a variety of species, the values of the model parameters are generally species dependent. Two approaches, allometric and physiologic, may be used to adjust or scale the values of model parameters determined for a substance in one species to predict its pharmacokinetic behavior in other species. In this paper, the allometric approach is applied to pharmacokinetic parameters determined by using compartmental models or "model-independent" methods. Model parameters (Pi) such as mean systemic clearance and steady-state apparent volume of distribution are of interest. Parameter values are determined in several species that vary significantly in body weight (BW). Values of the parameters frequently follow the power function of body weight: Pi = a(BW)b. Interspecies scaling is accomplished in that values of Pi for other species are then estimated from the body weights of those species.