Preclinical drug metabolism programs for food-producing animals

To register a new veterinary drug for use in food-producing animals, the sponsor must demonstrate that drug-related residues in the edible tissues (liver, kidneys, muscle, fat, and milk or eggs) of treated animals are safe when consumed by humans. The sponsor must develop information on the amount, persistence, and chemical nature of the drug-derived residue in the edible tissues in order to ensure safety. This information is compared to that on the metabolism and toxicity of the compound in the laboratory animal species used for the toxicity evaluation. The toxicity data is utilized to establish the safe concentration of drug-related residue in the edible tissues. An estimate of the safe concentration is necessary to proceed with residue studies that will adequately determine the rate of depletion of total residue over the projected range of probable safe concentrations. Appropriate study design requires close communication among the toxicologist, pathologist, and residue chemist. The safe concentration of total residue and residue depletion profile are used to determine the withdrawal period for the veterinary product. The required studies, including design and timing, will be discussed.