Comparative pharmacokinetics and the evaluation of human food safety for veterinary drugs

The evaluation of human food safety for veterinary drugs used in food animals is required as part of the veterinary drug approval process in most countries.Two elements necessary to demonstrate human food safety are toxicology data concerning the acute and chronic toxicity of the parent drug and its metabolites,and data describing the pharmacokinetics of residues of the drug and metabolites in the species of animals in which the drug will be used.Interspecies differences in metabolism can be qualitative and quantitative.In most food animals,qualitative differences in metabolism of veterinary drugs is not seen.Differences are almost always in the amounts of individual metabolites and their distribution.Because residues are composed of the parent drug and metabolites,interspecies comparisons must involve consideration of comparative xenobiotic metabolism.Aspects of comparative food animal drug metabolism which can afect the composition of residues will be reviewed.Additionally,the residue studies which are required to establish human food safety,and interspecies differences and similarities in the pharmacokinetics of drugs which impact residues of drugs in animal derived foods will be studied.To illustrate the factors which can complicate and assist these comparisons,two drugs will be examined in detail;ivemectin and fenbendazole.The results of recent residue studies exploring comparative pharmacokinetics and metabolism in avian species will be presented.Lastly,the activities of two US programs,FARAD and The NRSP-7 Minor Use Animal Drug Program,which routinely address interspecies comparisons will be presented along with potential strategies which may be employed in the study of species diffecences.