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Mixed-effects modeling of the interspecies pharmacokinetic scaling of oxytetracycline

✍ Scribed by Tomás Martín-Jiménez; Jim E. Riviere


Book ID
102399820
Publisher
John Wiley and Sons
Year
2002
Tongue
English
Weight
147 KB
Volume
91
Category
Article
ISSN
0022-3549

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✦ Synopsis


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 coef®cients and exponents of the pharmacokinetic parameters to obtain a model that best ®ts the multi-species pooled concentration±time data. Furthermore, this approach allows decisions to be made based on the statistical signi®cance of the parameter estimates and the adequacy of the models that are not possible with traditional approaches.


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