AJP - Regulatory, Integrative and Comparative Physiology, Vol 245, Issue 6 768-R775, Copyright © 1983 by American Physiological Society
Interspecies pharmacokinetic scaling and the Dedrick plots
H. Boxenbaum and R. Ronfeld
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.
