Species scaling of propafenone disposition and concentration‐time relationships among eight mammalian species

Usually, smaller mammals have higher clearances per unit body mass than do larger mammalian species. When clearance and other pharmacokinetic parameters are correlated with internal physiological processes, species tend to dispose of drugs at a similar pace. The first application of this concept is pharmacokinetic time, expressed with different units: Kallynochron, Apolysichron, Dienetichron, and Syndesichron. The present work describes pharmacokinetic time in these units from data obtained with propafenone in eight animal species: mouse, rat, rabbit, dog, sheep, human, cow, and horse. Additionally, volume of distribution (Vdss = 6.5 B0.94) and clearance (CL = 0.17 B0.86) were correlated to body weight (B). Different units of pharmacokinetic time were evaluated with an Akaike Information Criterion test, and the Syndesichron was the unit that provided the best superimposition for the concentration‐time plot for all animal species. It can be inferred that all mammalian species eliminated half of the dose from their bodies in 4759 Syndesichrons. Copyright © 1993 Wiley‐Liss, Inc., A Wiley Company