Interspecies scaling of interferon disposition and comparison of allometric scaling with concentration-time transformations
Abstract
Interspecies scaling is used to extrapolate pharmacokinetic parameters from animals to humans, through the application of physiologically based models, by empirical allometric procedures, or using concentration-time transformations. The aim of this study was to compare the accuracies of the last two methods for predicting the pharmacokinetic parameters and concentration-time curves in humans. In the first part of this study, interspecies scaling techniques were applied to a hypothetical drug (extracellular distribution and elimination through glomerular filtration), to examine the influence of various laboratory animals (mouse, rat, cynomolgus monkey and dog) on the parameters predicted for man. The same techniques were also applied to interferon-alpha A, using the literature data for various animal species. The kinetic parameters predicted in man were then compared to the values published for man. Our theoretical example showed that, for allometric scaling, each species has a very different influence on the prediction in human. With the approach using concentration-time transformations, however, each animal species potentially makes a similar contribution to the prediction for man. Based on the pharmacokinetic data published f...Continue Reading
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Accuracy of allometrically predicted pharmacokinetic parameters in humans: role of species selection
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