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Drug Metabolism and Disposition Fast Forward
First published on May 26, 2005; DOI: 10.1124/dmd.105.004135

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Received for publication February 10, 2005.
Revised May 19, 2005.
Accepted for publication May 20, 2005.

A Mathematical Description of the Functionality of Correction Factors Used in Allometry for Predicting Human Drug Clearance

Huadong Tang 1 Michael Mayersohn 1*

1 University of Arizona

* Address correspondence to: E-mail: mayesohn{at}pharmacy.arizona.edu

Abstract

The functionality of the correction factors, maximum life-span potential (MLP) and brain weight (BrW) used in allometry, is mathematically described. Correction by MLP or BrW is equivalent to a multiplication of some constants by the predicted values in humans from simple allometry, but they have no relationship to measured pharmacokinetic parameters in the animal species. The values of these constants (FMLP or FBrW) were calculated for some commonly used combinations of animal species. For all combinations of animal species, the value of FBrW is always greater than FMLP with a fold-increase of about 1.3 to 1.9. Different combinations of species give different values of FBrW and FMLP. In addition, the role of correction factors (MLP and BrW) or the "rule of exponents" (ROE) was evaluated. An intrinsic defect in using correction factors or ROE was revealed; different study designs will produce significantly different prediction results. However, ROE may still serve as a useful practical approach in predicting human CL since it was derived from real observations and has been applied to many examples.


Key words: drug clearance, in vitro-in vivo scaling, pharmacokinetics


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