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. Following 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 concentrations 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 postdose. The residue levels found in liver (135, 50, and 17 ppb), kidney (41, 22, and <4 ppb), and loin muscle were 25, 12, and <4 ppb, respectively. Fecal excretion was the major elimination pathway and accounted for 52%, while urinary excretion accounted for <1% of the administered dose. The extremely low residues in edible tissues precluded metabolite isolation in sufficient quantities for spectroscopic identification. 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 feces by LC/MS and LC/MS/MS. Sheep liver in vitro metabolism studies permitted isolation of the major metabolite, whose identity was unequivocally established by LC/MS, LC/MS/MS, and NMR as the C-29/30 monohydroxymethyl derivative of moxidectin.