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

The absorption, tissue distribution, metabolism, and excretion of moxi dectin, a new endectocide for the control of internal and external par asites in cattle and sheep, was studied in cattle. - Following a singl e subcutaneous dose of C-14- and H-2-labeled moxidectin of 0.2 mg/kg o f body weight, highest C-14 residues were present in abdominal fat (89 8, 636, and 275 ppb) and back fat (495, 424, and 186 ppb) at 7, 14, an d 28 days posttreatment, respectively. Lower residues were detected in liver (109, 77, and 31 ppb), kidney (42, 38, and 13 ppb), and loin mu scle (21, 10, and 4 ppb), respectively. The administered radioactivity was excreted primarily in the feces, with only 3% of the dose being e liminated in the urine. The HPLC/C-14 profiles of the residues extract ed from the tissues, fat, and feces were qualitatively similar and sho wed moxidectin was the major component of the residue. Only two metabo lites were present that were more than 5% (2 ppb) of the total liver r esidues 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 authe ntic compounds prepared in-vitro from cattle liver microsomal incubati on and rat liver homogenate incubation with C-14-labeled moxidectin co nfirmed the mass spectral results. By LC/MS and LC/MS/MS, several othe r mono- and dihydroxylated and O-demethylated metabolites were also id entified.