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Drug Metabolism and Disposition Fast Forward
First published on June 15, 2005; DOI: 10.1124/dmd.105.004143

0090-9556/05/3309-1297-1303$20.00
DMD 33:1297-1303, 2005

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A NOVEL MODEL FOR PREDICTION OF HUMAN DRUG CLEARANCE BY ALLOMETRIC SCALING

Huadong Tang1, and Michael Mayersohn

Department of Pharmaceutical Sciences, College of Pharmacy, The University of Arizona, Tucson, Arizona

Sixty-one sets of clearance (CL) values in animal species were allometrically scaled for predicting human clearance. Unbound fractions (fu) of drug in plasma in rats and humans were obtained from the literature. A model was developed to predict human CL: CL = 33.35 ml/min x (a/Rfu)0.770, where Rfu is the fu ratio between rats and humans and a is the coefficient obtained from allometric scaling. The new model was compared with simple allometric scaling and the "rule of exponents" (ROE). Results indicated that the new model provided better predictability for human values of CL than did ROE. It is especially significant that for the first time the proposed model improves the prediction of CL for drugs illustrating large vertical allometry.

Address correspondence to: Michael Mayersohn, College of Pharmacy, The University of Arizona, 1703 East Mabel Street, Tucson, AZ 85721. E-mail: mayersohn{at}pharmacy.arizona.edu




This article has been cited by other articles:


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 Drug Metab. Dispos.Home page
H. Tang, A. Hussain, M. Leal, M. Mayersohn, and E. Fluhler
Interspecies Prediction of Human Drug Clearance Based on Scaling Data from One or Two Animal Species
Drug Metab. Dispos., October 1, 2007; 35(10): 1886 - 1893.
[Abstract] [Full Text] [PDF]

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 J Clin PharmacolHome page
H. Tang and M. Mayersohn
On the Observed Large Interspecies Overprediction of Human Clearance ("Vertical Allometry") of UCN-01: Further Support for a Proposed Model Based on Plasma Protein Binding.
J. Clin. Pharmacol., April 1, 2006; 46(4): 398 - 400.
[Abstract] [Full Text] [PDF]


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