Interspecies scaling: predicting clearance of drugs in humans. Three different approaches.
1. The interspecies scaling approach to predict clearance in humans from animal data was tested for a wide variety of drugs. 2. Three different methods were utilized to generate plots to scale-up the clearance values: (i) method I, clearance versus body weight (simple allometric equation); (ii) method II, product of clearance and maximum life-span potential; (iii) method III, product of clearance and brain weight versus body weight. 3. The circumstances under which the three methods can be applied to predict clearance in humans were evaluated. 4. If the exponent lies between 0.55 to 0.7 then method I predicts clearance reasonably well. 5. If the exponent lies between 0.71 to 1.0 clearance can be predicted reasonably well by method II. 6. If the exponent is > 1.0 clearance can be predicted using method III.
Mahmood
I
I
Division of Pharmaceutical Evaluation I. Food & Drug Administration, Rockville, MD 20852, USA.
Balian
J D
JD
D000818:Animals; D006801:Humans; D008433:Mathematics; D008657:Metabolic Clearance Rate; D010599:Pharmacokinetics; D013045:Species Specificity