INTERSPECIES EXTRAPOLATION OF PHARMACOKINETICS

The purpose of this paper is to use physiologically based pharmacokinetic models to demonstrate that if toxic response is a function of the time profile in physiological time of the concentration of the toxic moiety in the target tissue, then the appropriate interspecies scaling law for toxic compounds which are metabolically deactivated is mg kg-1 per unit of physiological time (mg kg-1 pt-1). At low dose rates this metric is approximately equivalent to mg kg-0.75 dayt-1. For reactive metabolites which are spontaneously deactivated, an approximate interspecies scaling law is mg kg-1 day-1. © 1990 Academic Press Limited.