Role of the cytochrome P450 enzyme system in veterinary pharmacokinetics: where are we now? Where are we going?

Abstract

Drug metabolism is a core determinant of the dose–effectiveness–toxicity relationship of many compounds. It is also critical to the human food safety assessment of drug residues in the edible tissues of food-producing animals. This article describes the current state of knowledge regarding the role of the cytochrome P450 superfamily of enzymes in determining the metabolic profile of compounds administered to companion animals (e.g., dog and cat) and to food-producing animal species (e.g., cattle, swine, chickens). In turn, this knowledge reflects the collection of insights derived from the recognized population variability observed in human drug metabolism, our general understanding of the kinetics of various drug-metabolism pathways, emerging tools that enable the role of pharmacogenetics to be studied and the characterization of drug metabolism in individual veterinary species. Ultimately, by increasing our insights with regard to factors that can influence drug metabolism, our knowledge of metabolic pathways, sources of within- and between-species variability in pharmacokinetics and the development of in silico models that can be used to predict pharmacokinetic profiles from these diverse sources of information. We will improve our ability to generate the population inferences needed to insure the target animal safety, product effectiveness and the human food safety of veterinary pharmaceuticals.