A comparative study of allometric scaling with plasma concentrations predicted by species-invariant time methods

Citation
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
Citations number
24
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOPHARMACEUTICS & DRUG DISPOSITION
ISSN journal
01422782 → ACNP
Volume
20
Issue
3
Year of publication
1999
Pages
137 - 144
Database
ISI
SICI code
0142-2782(199904)20:3<137:ACSOAS>2.0.ZU;2-4
Abstract
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.