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SHORT COMMUNICATION

Utility of the Coefficient of Determination (r²) in Assessing the Accuracy of Interspecies Allometric Predictions: Illumination or Illusion?

Bioanalytical R&D, Drug Safety and Metabolism, Wyeth Research, Pearl River, New York (H.T.); and Department of Pharmaceutical Sciences, College of Pharmacy, The University of Arizona, Tucson, Arizona (M.M.)

The appropriateness of relying on the coefficient of determination (r²) as a statistical metric for judging the predictability of human clearance (CL) based on interspecies animal data was assessed. An explicit mathematical expression was derived for r² as a function of species body weight and the corresponding measured value of CL. The derived mathematical function demonstrated that r² is numerically large in most instances. Simulations using random CL generated from a common combination of species of mouse, rat, and monkey resulted in an r² of 0.75 as the minimum, and 0.95 and 0.98 at 50th and 75th percentiles, respectively, given that total CL values increase with increasing species body weight. Analysis of literature data also indicated that the prediction accuracy of human CL was not correlated with values of r². Therefore, it is concluded that r² is a limited statistical measure when assessing allometric scaling for the purpose of predicting human CL.