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Population variability in animal health: Influence on dose–exposure–response relationships: Part I: Drug metabolism and transporter systems
Authors:Marilyn N Martinez  Michael H Court  Johanna Fink‐Gremmels  Katrina L Mealey
Institution:1. Center for Veterinary Medicine, US Food and Drug Administration, Rockville, MarylandCommunicating authorThis article reflects the views of the author and should not be construed to represent FDA's views or policies.;2. Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington;3. Division of Pharmacology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands
Abstract:There is an increasing effort to understand the many sources of population variability that can influence drug absorption, metabolism, disposition, and clearance in veterinary species. This growing interest reflects the recognition that this diversity can influence dose–exposure–response relationships and can affect the drug residues present in the edible tissues of food‐producing animals. To appreciate the pharmacokinetic diversity that may exist across a population of potential drug product recipients, both endogenous and exogenous variables need to be considered. The American Academy of Veterinary Pharmacology and Therapeutics hosted a 1‐day session during the 2017 Biennial meeting to explore the sources of population variability recognized to impact veterinary medicine. The following review highlights the information shared during that session. In Part I of this workshop report, we consider sources of population variability associated with drug metabolism and membrane transport. Part II of this report highlights the use of modeling and simulation to support an appreciation of the variability in dose–exposure–response relationships.
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