Interspecies pharmacokinetic scaling and the Dedrick plots

Abstract

Interspecies variations in pharmacokinetics are frequently the consequence of organisms living in different time domains. Whereas species' parameter values differ when referenced to chronological time, scaling of data with respect to active mass (ergosomes) and to ideal (mathematical) pharmacokinetic space time (mesochrons, kallynochrons, or apolysichrons) removes the astronomical time dependency. A theory of pharmacokinetic similarities is presented which states that both physiological and pharmacokinetic processes are biologically interrelated and governed by a master synchronization mechanism; consequently interspecies pharmacokinetic events frequently may be expressed as invariant values; e.g., hexobarbital disposition half-life is approximately the duration of 1,680 gut beats (time standard) regardless of mammalian species. The depletion theory hypothesis of aging that each mammalian organism of set mass is genetically endowed with a set total energy or metabolism (lebenszeitliche Kraft) is found to be adaptable at the microscopic pharmacokinetic level; thus it is hypothesized that each mammalian organism has a genetically determined and finite quantity of phase I hepatic pharmacokinetic stuff (activity) to expend during a lifetime and that this pharmacokinetic stuff (ml cleared X kg-1 X maximum life-span potential-1) is a constant. The rate at which this pharmacokinetic stuff is utilized (comparative pharmacokinetics) is presumed to be regulated by a pharmacokinetic clock, which may undergo either acute or chronic perturbations having either a genetic or environmental origin.