Binding of ractopamine HCl to ocular tissues of cattle and turkeys in vivo and to melanin in vitro.

Abstract

Experiments were conducted to determine the total residues remaining in ocular tissues of cattle and turkeys after oral administration of [14C]ractopamine HCl. Twelve cattle were intraruminally dosed with 0.9 mg x kg(-1) x d(-1) of [14C]ractopamine HCl for 7 d. Four cattle each were slaughtered with withdrawal periods of 48,96, and 144 h. Radioactive residues were not detectable in whole-eye homogenates from the cattle. Eight male and eight female turkeys per treatment received either 7.5, 22.5, or 30 ppm dietary [14C]ractopamine HCl (0.33, 1.02, and 1.36 mg x kg(-1) x d(-1); treatment groups 1, 2, and 3, respectively) for 7 d, and the birds were slaughtered with a 0-d withdrawal period. Eyes were dissected into retina/choroid/schlera (RCS), cornea/iris (CI), and aqueous humor (AH) fractions. Residues in RCS, CI, and AH of treatment 1 turkeys were not detectable. Residues in AH were < 0.02 ppm in treatment groups 2 and 3. Mean residues in RCS ranged from 0.15 to 0.26 ppm, and mean CI residues ranged from <0.09 to 0.17 ppm for treatment groups 2 and 3, respectively. The propensities of ractopamine and synthetic ractopamine metabolites to bind to melanin were studied in vitro using radiolabeled ligands with centrifugal filtration to separate melanin from unbound ligand. In vitro studies showed that [14C]ractopamine HCl binds to melanin rapidly and was displaced from melanin by other beta-agonists. Glucuronidation of ractopamine, which produced the major biotransformation product of ractopamine in all species studied to date, prevented binding to melanin. These studies demonstrate that the propensity for the in vivo binding of ractopamine HCl to pigmented ocular tissues is less than that reported for clenbuterol.