MOXIDECTIN - ABSORPTION, TISSUE DISTRIBUTION, EXCRETION, AND BIOTRANSFORMATION OF C-14-LABELED MOXIDECTIN IN SHEEP

The absorption, tissue distribution, excretion, and biotransformation of moxidectin, a novel endectocide that combats internal and external parasites in sheep, cattle, and horse, were studied in sheep. Followin g a single oral administration of a 1:1 mixture of C-14- and deuterium -labeled moxidectin at 0.2 mg/kg of body weight, the highest residue c oncentrations among the edible tissues were observed in fat (249, 305, and 118 ppb; average of omental and back fat) at 1, 7, and 28 days po stdose. The residue levels found in liver (135, 50, and 17 ppb), kidne y (41, 22, and <4 ppb), and loin muscle were 25, 12, and <4 ppb, respe ctively. Fecal excretion was the major elimination pathway and account ed for 52%, while urinary excretion accounted for <1% of the administe red dose. The extremely low residues in edible tissues precluded metab olite isolation in sufficient quantities for spectroscopic identificat ion. Since the metabolite profile in feces is similar to that observed in liver, one major (monohydroxylated) and at least six minor (mono, dihydroxylated, O-demethylated) metabolites were characterized from fe ces by LC/MS and LC/MS/MS. Sheep liver in vitro metabolism studies per mitted isolation of the major metabolite, whose identity was unequivoc ally established by LC/MS, LC/MS/MS, and NMR as the C-29/30 monohydrox ymethyl derivative of moxidectin.