Moxidectin:  Metabolic Fate and Blood Pharmacokinetics of¹⁴C-Labeled Moxidectin in Horses

Serum and whole blood pharmacokinetics of moxidectin and excretion and biotransformation in edible tissues and excreta have been evaluated in the horse at a dose level of 0.4 mg/kg of body weight. Three animals were orally dosed with C-14-labeled moxidectin, formulated as a gel. Total radioactive residues (TRR) were determined in whole blood and in serum collected at selected intervals through 168 h. Sera samples were also assayed for intact moxidectin. At 168 h, animals were sacrificed and TRR determined in edible tissues, namely muscle, liver, kidney, and fat. The mean terminal elimination half-lives for total radioactivity and parent in serum were 154 +/- 26 and 82 +/- 23 h, respectively. Fecal excretion was the main elimination pathway, accounting for 77% of the administered dose by 168 h. Although minor metabolites were noted, intact parent was the major component in tissues and excreta. Similarly, three animals were intravenously (iv) dosed with C-14-labeled moxidectin, formulated as an aqueous injectable solution. The terminal elimination half-lives for total radioactivity and intact parent in serum were 128 +/- 14 and 81 +/- 18 h, respectively. On the basis of a comparison of intact parent area under the concentration/time (AUG) values of 4.55 and 11.4 mu g.h/g following oral and iv doses, respectively, an oral bioavailability of approximately 40% was estimated.