Mixed-effects modeling of the interspecies pharmacokinetic scaling of oxytetracycline.

Differences in the disposition of certain drugs across mammalian species often arise because of their diverse physiology and anatomical characteristics. Factors such as body mass, brain weight, and maximum lifespan are related to the way that different species of mammals handle drugs. Drug disposition data can be scaled across species when chronological time is substituted by the appropriate measure of pharmacokinetic time. In this study, we developed allometric scaling models for oxytetracycline, using serum disposition data obtained from the Food Animal Residue Avoidance Databank. The data were modeled using the mixed-effects modeling approach. The models obtained were validated using disposition data on swine. Oxytetracycline scaled across species based on body weight and the best interspecies model adequately predicted the value of the pharmacokinetic parameters across species. The population approach allows one to estimate the allometric coefficients and exponents of the pharmacokinetic parameters to obtain a model that best fits the multi-species pooled concentration-time data. Furthermore, this approach allows decisions to be made based on the statistical significance of the parameter estimates and the adequacy of the models that are not possible with traditional approaches. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:331-341, 2002