A comparative study of allometric scaling with plasma concentrations predicted by species-invariant time methods.
The objective of this study is to compare the empirical allometric approaches with species invariant time methods using equivalent time, kallynochron, apolysichron, and dienetichrons. Pharmacokinetic parameters (clearance, volume of distribution, and elimination half-life) of ethosuximide, cyclosporine and ciprofloxacin were scaled-up from animal data obtained from the literature. Two methods were utilized to generate plots for the prediction of clearance in humans: (i) clearance versus body weight (simple allometric equation); and (ii) the product of clearance and maximum life-span potential (MLP) versus body weight. Plasma concentrations of each of the drugs were predicted using elementary and complex Dedrick plots, equivalent time with an exponent of 0.25 and equivalent time with the exponent obtained from the plot of body weight and half-life. Plasma concentrations of cyclosporine and ciprofloxacin were also predicted by MLP normalization (dienetichrons). Almost similar results in the pharmacokinetic parameters of the tested drugs were obtained by the allometric approach and by the species invariant time methods.
Mahmood
I
I
Office of Clinical Pharmacology and Biopharmaceutics, Division of Pharmaceutical Evaluation I (HFD-860), Food & Drug Administration, Rockville, MD 20852, USA. Mahmoodi@CDER.FDA.GOV
Yuan
R
R
D000818:Animals; D001835:Body Weight; D006207:Half-Life; D006801:Humans; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010599:Pharmacokinetics