Pharmacokinetic profile, tissue residue depletion and anthelmintic efficacy of supramolecular fenbendazole.

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.

Influence of mechanochemical technology on anthelmintic efficacy of the supramolecular complex of fenbendazole with polyvinylpyrrolidone.

OBJECTIVE: The purpose of our research was to evaluate the effect of mechanochemical technology on the efficacy of supramolecular complex of fenbendazole (SMCF) with polyvinylpyrrolidone (PVP) polymer against some helminthosis of animals. MATERIALS AND METHODS: The SMCF samples with PVP were synthesized using a solid-state mechanochemical technology in activators of impact-abrading type and their physicochemical properties were analyzed. The efficacy of SMCF was studied on the laboratory model of Hymenolepis nana and Trichinella spiralis infection of mice and helminthosis of sheep. RESULTS: In the trials conducted on laboratory models, the supramolecular complex showed 93.94% and 98.56 % efficacy at the dose of 1 mg/kg of body weight (b/w), while the substance of fenbendazole showed 7.97% and 8.33% efficacy at the same dose. A high efficacy (>94%) of the SMCF was revealed at the dose of 2.0 mg/kg of b/w at oral administration against nematodes in naturally infected sheep by the results of the fecal examination, while the substance of fenbendazole was active at the dose of 5.0 mg/kg at single oral administration. Moreover, the SMCF demonstrated 97.37% efficacy at the dose of 2 mg/kg against Moniezia spp. infection of sheep. Physicochemical studies confirmed the increase in solubility of the complex, reducing of particle sizes, amorphization of fenbendazole substance, and incorporating it with micelles of PVP. CONCLUSION: According to the results, supramolecular complex of fenbendazole with PVP was more active than the basic substance of fenbendazole and its anthelmintic properties were expanded.

The efficacy of the supramolecular complexes of niclosamide obtained by mechanochemical technology and targeted delivery against cestode infection of animals.

Niclosamide is an anthelmintic that is widely used to treat cestode infection of animals. The efficacy of the supramolecular complexes of niclosamide obtained by mechanochemical technology and targeted delivery was studied in hymenolepiosis of mice and monieziosis of sheep. The efficacy of new substances of niclosamide with polyvinylpyrrolidone polymer in different ratios (1:10; 1:5; 1:2) was determined by the results of helminthological necropsy of the small intestine of sheep and mice. Pre-treatment eggs per gram (EPG) were not significantly different (P>0.1) among groups. The controlled test was used to evaluate the efficacy. A high efficacy (>95% efficacy) of the supramolecular complexes of niclosamide with PVP (SCoNwPVP) was shown in different ratios (1:10; 1:5 and 1:2) at a dose of 20mg/kg of body weight at oral administration against Hymenolepis nana in mice and Moniezia expansa in sheep. Whereas the basic drug - substance of niclosamide was effective at a dose of 100mg/kg of b/w. No adverse effects of the drugs on animal health were detected during the study.

A Physicochemical and Pharmacological Study of the Newly Synthesized Complex of Albendazole and the Polysaccharide Arabinogalactan from Larch Wood.

Inclusion complexes of albendazole (ABZ) with the polysaccharide arabinogalactan from larch wood Larix sibirica and Larix gmelinii were synthesized using a solid-state mechanochemical technology. We investigated physicochemical properties of the synthesized complexes in the solid state and in aqueous solutions as well as their anthelmintic activity against Trichinella spiralis, Hymenolepis nаna, Fasciola hepatica, Opisthorchis felineus, and mixed nematodoses of sheep. Formation of the complexes was demonstrated by means of intrinsic solubility and the NMR relaxation method. The mechanochemically synthesized complexes were more stable in comparison with the complex produced by mixing solutions of the components. The complexes of ABZ showed anthelmintic activity at 10-fold lower doses than did free ABZ. The complexes also showed lower acute toxicity and hepatotoxicity. These results suggest that it is possible to design new drugs on the basis of the ABZ:arabinogalactan complex that are safer and more effective than albendazole.