The Pharmacokinetics, Metabolism, and Tissue Residues of b-Adrenergic Agonists in Livestock1,2

Since the early 1980s the usefulness of dietary b-agonists to improve the efficiency of feed utilization and(or) to enhance carcass leanness in livestock species has been well documented. Less well documented are the pharmacokinetic properties, biotransformation pathways, and tissue residue profiles of b-agonists used to enhance leanness in experimentally or illegally treated animals. Pharmacokinetic data for clenbuterol, cimaterol, fenoterol, L-644,969, ractopamine, salbutamol, and terbutaline have been published but biotransformation and tissue residue studies for these compounds in livestock species are sparse. In general, b-agonists having halogenated aromatic ring systems are metabolized by oxidative and conjugative pathways and have long plasma halflives, whereas b-agonists having hydroxylated aromatic rings are metabolized solely by conjugation and have relatively short plasma half-lives. b-Agonists having high oral bioavailabilities, long plasma halflives, and relatively slow rates of elimination have high oral potencies in humans. Residues of such illegally used compounds in edible tissues of livestock represent a genuine risk to consumers. Conversely, bagonists having low oral bioavailabilities, short plasma half-lives, and rapid rates of elimination have low oral potencies in humans. Residues of such compounds in edible tissues of properly treated animals would not likely represent a credible risk to consumers of such products. The reviewed data indicate that the development of a safe and effective bagonist for use in livestock is possible.