METABOLISM AND DISPOSITION OF RACTOPAMINE HYDROCHLORIDE BY TURKEY POULTS

Ractopamine HCl, enyl)-1-methylpropyl]-amino]methyl]benzenemethanol hy drochloride), is a beta-adrenergic agonist that is under evaluation as a nutrient repartitioning agent in livestock. Because ractopamine met abolism has not been evaluated in turkeys, the objectives of this stud y were to synthesize and identify products of ractopamine metabolism a nd to determine the stereoselective metabolism and tissue distribution of [C-14]ractopamine HCl in orally dosed turkey poults. Glucuronides of diastereoisomeric [C-14]ractopamine, and the (1R,3R) and (1R,3S) st ereoisomers of ractopamine were synthesized by use of microsomal prote ins immobilized on Sepharose beads. Monoglucuronides conjugated to the phenols at C-10 or C-10' were isolated and identified by H-1-NMR and negative ion FAB/MS. Urine and feces were collected from colostomized turkey poults after oral dosing with 20 Mg of [C-14]ractopamine HCl (9 .28 muCi). Radioactive residues in tissues were highest in the gallbla dder and liver. Radioactivity was not detectable in blood 48 hr after dosing and was slightly above background (<100 dpm/g tissue) in skelet al and cardiac muscle. Urine contained 47.5% of the administered radio activity by 16 hr after dosing, and by 48 hr 52.0% of the radioactivit y was excreted in the urine. Feces contained 36.6% and 41.5% of the do se 16 and 48 hr after dosing, respectively. Unmetabolized ractopamine represented only 8% of the urinary radioactivity; ractopamine glucuron ides represented 72% of the urinary radioactivity. Glucuronides conjug ated to the C-10 phenol of ractopamine represented 59.8% of the urinar y metabolites and were composed of all four ractopamine stereoisomers. Glucuronides conjugated to the C-10' phenol of ractopamine represente d 12.7% of the urinary metabolites and were composed of the (1R,3R) an d (1R,3S) stereoisomers. Ractopamine was rapidly eliminated from turke ys after oral dosing, and glucuronidation was the major pathway of met abolism. Regioselective glucuronidation occurred favoring the C-10 phe nol of ractopamine; glucuronidation of the C-10' phenol of ractopamine was specific for the (1R,3R) and (1R,3S) stereoisomers.