ABSORPTION, TISSUE DISTRIBUTION, METABOLISM, AND EXCRETION OF MOXIDECTIN IN CATTLE

The absorption, tissue distribution, metabolism, and excretion of moxidectin, a new endectocide for the control of internal and external parasites in cattle and sheep, was studied in cattle. - Following a single subcutaneous dose of C-14- and H-2-labeled moxidectin of 0.2 mg/kg of body weight, highest C-14 residues were present in abdominal fat (898, 636, and 275 ppb) and back fat (495, 424, and 186 ppb) at 7, 14, and 28 days posttreatment, respectively. Lower residues were detected in liver (109, 77, and 31 ppb), kidney (42, 38, and 13 ppb), and loin muscle (21, 10, and 4 ppb), respectively. The administered radioactivity was excreted primarily in the feces, with only 3% of the dose being eliminated in the urine. The HPLC/C-14 profiles of the residues extracted from the tissues, fat, and feces were qualitatively similar and showed moxidectin was the major component of the residue. Only two metabolites were present that were more than 5% (2 ppb) of the total liver residues after 28 days. These were-identified as the C-29/30 and the C-14 monohydroxymethyl metabolites by LC/MS and LC/MS/MS analysis of the metabolites isolated from the feces. Proton NMR analysis of the authentic compounds prepared in-vitro from cattle liver microsomal incubation and rat liver homogenate incubation with C-14-labeled moxidectin confirmed the mass spectral results. By LC/MS and LC/MS/MS, several other mono- and dihydroxylated and O-demethylated metabolites were also identified.