FACTORS THAT AFFECT DRUG DISPOSITION IN FOOD-PRODUCING ANIMALS DURING MATURATION

Drugs administered to neonatal food-producing animals (cattle, sheep, goats, swine) may exhibit significantly different pharmacokinetic/disposition characteristics than they do in adult animals of the same species. Undesirable consequences such as suboptimum therapeutic concentrations, toxic effects, and violative tissue residues may result if adult dosage regimens are employed in young animals. Using selected drugs as examples, this paper reviews factors that contribute to differences in drug disposition in newborn vs adult animals. Immaturity of mechanisms involved in drug absorption, especially from gastrointestinal and parenteral sites of administration, and of drug distribution to sites such as plasma proteins, adipose tissue, and fluid compartments are considered. The role of developmental changes in drug biotransformation in the liver and other tissues and the maturation of excretory mechanisms, primarily from the kidney, in the increased rate of drug clearance during maturation is described. Pharmacokinetic studies with specific drugs in the target species are an important approach to establishing rational drug use in immature food-producing animals.