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Drug Metabolism and Disposition Fast Forward
First published on May 26, 2005; DOI: 10.1124/dmd.105.004127

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

Accuracy of allometrically-predicted pharmacokinetic parameters in humans- Role of species selection

Huadong Tang 1 Michael Mayersohn 2*

1 The University of Arizona 2 University of Arizona

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

Abstract

A general equation was derived, which directly describes the mathematical relationship between the allometrically-predicted pharmacokinetic (PK) parameters in humans and the body weights of animal species (along with their corresponding measured PK parameters). It was shown, with use of the derived equation, that the predicted values in humans, based on combinations of animal species commonly used in allometry, are heavily dependent on certain species, for example, the dog. In contrast, parameter values from the rat made no contribution to the predicted human values, as long as the rat was not the smallest species used. Monte Carlo simulations were further performed to examine the species or weight dependency. The cost-effective combinations of animal species, in term of number and species type, were theoretically examined through simulations. Finally, literature data demonstrated the species or weight dependency predicted from the equation and as illustrated through the Monte Carlo simulations. Appreciation of this species or weight dependency should guide researchers in selecting animal species and designing optimal experiments in the application of allometric scaling.


Key words: drug clearance, mathematical modeling, Monte Carlo simulations, pharmacokinetics


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