Biotransformation of fenbendazole in sheep after administration of fenbendazole solid dispersion prepared by mechanochemical technique with arabinogalactane

The purpose of the research is to study the biotransformation of fenbendazole in the body of sheep after administration of fenbendazole solid dispersion (FSD) prepared by mechanochemical technique with arabinogalactan. Materials and methods . The FSD at a dose of 2.0 mg/kg for the active substance was administered orally to sheep. Animal blood serum samples were studied by high performance liquid chromatography / tandem mass spectrometry (HPLC-TMS) to determine the concentration of fenbendazole (FBZ) and its sulfoxide and sulfone metabolites at 0, 1, 2, 4, 6, 8, 12, 24, 33, 48 and 72 hours after administered FSD and initial FBZ (substance). FBZ and its metabolite residual quantity in the organs and tissues of the sheep was determined at 1, 3, 6, 11, and 21 days after the drug administration. The prepared sample and validated method were described. Results and discussion . A significant difference was found in the metabolism, pharmacokinetics, and timing of the FBZ and its metabolite elimination after the base drug (FBZ substance) and FSD were administered to sheep in an equal dose of 2.0 mg/kg for the active substance. FBZ and its metabolites began to be detected in blood serum 2 hours after the FSD and 4 hours after the base FBZ. Pharmacokinetic parameters of FBZ and its metabolites characterize a higher drug concentration in the blood and a longer retention time in the circulation after the FSD as compared with the base drug parameters. The FBZ and its metabolite maximum concentration was found in the organs and tissues of the sheep that received the FSD on day 3 in the liver amount of 4862.3±296.2 ng/g of FBZ; 18243.5±486.1 ng/g of sulfoxide; and 2482.3±132.4 ng/g of sulfone; and tens of times lower concentration after the base FBZ on day 6. FBZ and its metabolites were not detected in the organs and tissues of the sheep on day 16 after the base FBZ, and on day 21 after the FSD.