Metabolism and Kinetics in the Regulation of Animal Drugs

Abstract

"Criteria and Procedures for Evaluating Assays for Carcinogenic Residues," popularly known as the "Sensitivity of the Method (SOM)" proposal for the regulation of animal drugs and feed additives, employs an initial analysis to determine whether a compound must meet the requirements as a suspect carcinogen or the requirements for general food safety (GFS). Metabolism and kinetics of drug depletion play an important role in the six-step procedure that is used for either set of regulatory criteria. The only significant difference that exists between the two sets of criteria is the degree of testing required. However, the difference will usually not be manifest until positive findings of carcinogenicity in the chronic studies in laboratory animals trigger a further evaluation of the metabolism of the drug or feed additive. For both SOM and GFS, metabolic information will be used to determine the appropriateness of the test species as well as to help select a compound for residue analysis. Residue depletion kinetics in the food animals also play an integral role in the selection of species-strains for toxicity testing selection as well as in the selection of the compound for residue analysis in food. Furthermore, depletion kinetics are used to set a safe withdrawal period. The development of guidelines is discussed.

Hepatic cytochrome P‐450 dependent drug metabolizing activity in rats, rabbits and several food‐producing species

“…Comparative drug metabolism studies in food-producing mammalian species are needed not only for evaluating safety and efficacy of therapeutic drugs but also to provide important insights into possible interspecies variations in xenobiotic metabolism (Weber, 1983;Gregus et al, 1983). Extrapolations of data on drug metabolism in laboratory species to goats, sheep, cattle and pigs are difficult since tremendous species differences in drug metabolism catalyzed by microsomal mixed function oxidases are known to exist.…”

In Vitro Hepatobiotransformation of Sulphadimethoxine in Laying Hens

“…An in vitro biotransformation study of SDM in laying hens is lacking as yet. Comparative studies among hens and other animals are needed not only for judging the efficacy and safety of therapeutic SDM, but also to provide the base data that clarifies possible inter‐species variations in drug metabolism (Gregus et al., 1983; Weber, 1983).…”