A supramolecular complex of fenbendazole (SFBZ) with polyvinylpyrrolidone (PVP) was created by mechanochemical processing to increase its anthelmintic efficacy and to reduce the dose of applied drugs. The aim of our research was to study the pharmacokinetic profile and tissue residue depletion of fenbendazole (FBZ) and its metabolites: sulfoxide and sulfone in sheep after SFBZ treatment by high-performance liquid chromatography with tandem mass spectrometric detection and to evaluate its efficacy against gastrointestinal strongylatosis of sheep in field trials. The results revealed that FBZ and its metabolites were detected in blood serum in 2 h after SFBZ administration and in 4-6 h after the administration of the basic - FBZ. Pharmacokinetic parameters of SFBZ and its metabolites were characterized by higher rate of absorption, concentration of the drug and longer retention times in the blood serum. The maximum concentration of FBZ and its metabolites was detected on the 3rd day in the organs and tissues of sheep that received SFBZ. Thus, in the liver, the content of FBZ was 4878.0 ng/g, sulfoxide and sulfone - 18682.4 and 2483.6 ng/g respectively while the indicators of the basic FBZ and its metabolites were tenfold lower. FBZ and its metabolites were not detected in the organs and tissues of sheep on the 16th day in animals treated with the basic drug and on the 21st day after SFBZ administration. In field trials SFBZ demonstrated a high anthelmintic activity against nematodosis of sheep. It showed 98.2% efficacy against nematodirosis and 99.0 % against other types of gastrointestinal strongylatosis at a dose of 2 mg/kg of active substance (a.s.). Efficacy of mechanical mixture and efficacy of FBZ substance was in 3.1-3.4 times lower in the same dose.
Keywords: Fenbendazole; Liquid chromatography; Mass spectrometry; Pharmacokinetics; Residues; Sheep; Supramolecular complex.
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