I. Mahmood et R. Yuan, A comparative study of allometric scaling with plasma concentrations predicted by species-invariant time methods, BIOPHARM DR, 20(3), 1999, pp. 137-144
The objective of this study is to compare the empirical allometric approach
es with species invariant time methods using equivalent time, kallynochron,
apolysichron, and dienetichrons. Pharmacokinetic parameters (clearance, vo
lume of distribution, and elimination half-life) of ethosuximide, cyclospor
ine and ciprofloxacin were scaled-up from animal data obtained from the lit
erature. Two methods were utilized to generate plots for the prediction of
clearance in humans: (i) clearance versus body weight (simple allometric eq
uation); and (ii) the product of clearance and maximum life-span potential
(MLP) versus body weight. Plasma concentrations of each of the drugs were p
redicted using elementary and complex Dedrick plots, equivalent time with a
n exponent of 0.25 and equivalent time with the exponent obtained from the
plot of body weight and half-life. Plasma concentrations of cyclosporine an
d ciprofloxacin were also predicted by MLP normalization (dienetichrons). A
lmost similar results in the pharmacokinetic parameters of the tested drugs
were obtained by the allometric approach and by the species invariant time
methods. Copyright (C) 1999 John Wiley & Sons, Ltd.