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INTRODUCTION: Prescribing fenbendazole medicated feed for pheasants in the USA is considered extra-label drug use under CPG Sec 615.115, and a safe estimated withdrawal interval (WDI) must be applied following administration to this minor food-producing species. This study sought to determine the pharmacokinetic and residue depletion profile for fenbendazole and its major metabolites to estimate a WDI for pheasants following fenbendazole administration as an oral medicated feed. METHOD: Pheasants (n = 32) were administered fenbendazole as an oral medicated feed (100 ppm) for 7 days. Fenbendazole, fenbendazole sulfoxide, and fenbendazole sulfone (FBZ-SO2) in liver and muscle samples were analyzed using HPLC-UV. Tissue WDIs were estimated using FDA, European Medicines Agency (EMA), and half-life multiplication methods for US poultry tolerances, EMA maximum residue limits, and the analytical limit of detection (LOD; 0.004 ppm). Terminal tissue elimination half-lives (T1/2) were estimated by non-compartmental analysis using a naïve pooled data approach. RESULTS: The tissue T1/2 was 14.4 h for liver, 13.2 h for thigh muscle, and 14.1 h for pectoral muscle. The maximum estimated withdrawal interval was 153 h (7 days) for FBZ-SO2 in pectoral muscle using the FDA tolerance method (95% confidence interval for the 99th percentile of the population), and the LOD as the residue limit. DISCUSSION: The results from this study support the use of FBZ-SO2 as the marker residue in the liver of pheasants and the provision of evidence based WDIs following the extra-label administration of fenbendazole medicated feed (100 ppm) for 7 days.

Fenbendazole is an antiparasitic drug widely used in veterinary medicine to treat parasitic infections caused in animals like cattle, horses, sheep, and dogs. Recently, it has been repositioned as a potential alternative for cancer treatment. However, it is a highly hydrophobic molecule (0.9 ug/mL), which can compromise its dissolution rate and absorption. Thus, this work aimed to apply a nanotechnological approach to improve drug solubility and dissolution performance. Fenbendazole nanoparticles stabilized by different poloxamers were obtained by lyophilization without cryoprotectants. The behavior of the drug in the solid state was analyzed by X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy. The nanosystems were also evaluated for solubility and dissolution rate. A long-term stability evaluation was performed for three years at room temperature. The yields of the lyophilization ranged between 75 and 81% for each lot. The nanoparticles showed a submicron size (< 340 nm) and a low polydispersity depending on the stabilizer. The physicochemical properties of the prepared systems indicated a remarkable amorphization of the drug, which influenced its solubility and dissolution performance. The drug dissolution from both the fresh and aged nanosystems was significantly higher than that of the raw drug. In particular, nanoparticles prepared with poloxamer 407 showed no significant modifications in their particle size in three years of storage. Physical stability studies indicated that the obtained systems prepared with P188, P237, and P407 suffered certain recrystallization during long storage at 25 °C. These findings confirm that selected poloxamers exhibited an important effect in formulating fenbendazole nanosystems with improved dissolution. [ABSTRACT FROM AUTHOR]

Hedgehogs, Erinaceus spp., are commonly admitted to rescue centres in European countries. However, there are still few studies on parasitological fauna and treatment possibilities, including for E. roumanicus. This study aimed to evaluate parasitism in 34 hedgehogs directly after their admission to the Budapest Zoo and Botanical Garden Wildlife Rescue Centre, as well as the efficacy of fenbendazole treatment. The Mini-Flotac method was used to quantitatively evaluate and assess the efficacy of treatment with fenbendazole (100 mg/kg PO. BID for 7 days) in five selected individuals. Faecal samples were analysed at D0 and D14 after the beginning of the treatment. Globally, the prevalence of positive animals was 76%. Capillaria spp. were the most prevalent (68%), while coccidia showed a prevalence of 32%. Considering the range of action of this benzimidazole, the treatment provided an efficacy of 100%, eliminating all forms of Capillaria spp. Considering the high number of hedgehogs admitted to rescue centres and the potential effects of parasitism in morbidity and mortality during recovery, it is essential to improve our knowledge with regard to the parasitological fauna of these species and to attain effective treatment protocols. [ABSTRACT FROM AUTHOR]

The purpose of the research is to study the anthelmintic efficacy of suspensions based on a combined solid dispersion of Fenbendazole and Niclosamide.Materials and methods. Mechanochemistry methods were used to prepare suspensions of Fenbendazole (FBZ) and Niclosamide (NSM) substances, in particular, liquid phase grinding of substances with additives (licorice extract, polyvinylpyrrolidone (PVP)) in water or in aqueous sodium carboxymethylcellulose (NaCMC) solution. The grinding was conducted in LE-101 roller mill at energy intensity of 1 g for 1 hour at a roll rotation speed of 60–70 rpm. The resulting suspension samples of combined FBZ and NSM dispersions were studied for cestodocidal activity on a laboratory model of hymenolepiosis of white mice that were infected at a dose of 200 infective Hymenolepis nana eggs per animal.Results and discussion. The 100% efficacy of a combined NaCMC-based drug suspension containing FBZ 13 mg and NSM 130 mg in 1 g of suspension was achieved at a dose of 20 mg/kg of NSM and 2 mg/kg of FBZ. The suspension based on licorice extract, NaCMC, and dioctyl sulfosuccinate sodium salt containing FBZ 18.6 mg and NSM 186 mg in 1 g of suspension at the same dose, i.e. 20 mg/kg of NSM and 2 mg/kg of FBZ showed 71.43% efficacy against H. nana. The suspension based on licorice extract and NaCMC containing FBZ 24.6 mg and NSM 246 mg in 1 g of suspension at the same dose showed a 62.0% effect against H. nana. The activity of the basic drug, the FBZ and NSM suspension was 28.58% at this dose without using mechano-chemical treatment.

Hedgehogs, Erinaceus spp., are commonly admitted to rescue centres in European countries. However, there are still few studies on parasitological fauna and treatment possibilities, including for E. roumanicus. This study aimed to evaluate parasitism in 34 hedgehogs directly after their admission to the Budapest Zoo and Botanical Garden Wildlife Rescue Centre, as well as the efficacy of fenbendazole treatment. The Mini-Flotac method was used to quantitatively evaluate and assess the efficacy of treatment with fenbendazole (100 mg/kg PO. BID for 7 days) in five selected individuals. Faecal samples were analysed at D0 and D14 after the beginning of the treatment. Globally, the prevalence of positive animals was 76%. Capillaria spp. were the most prevalent (68%), while coccidia showed a prevalence of 32%. Considering the range of action of this benzimidazole, the treatment provided an efficacy of 100%, eliminating all forms of Capillaria spp. Considering the high number of hedgehogs admitted to rescue centres and the potential effects of parasitism in morbidity and mortality during recovery, it is essential to improve our knowledge with regard to the parasitological fauna of these species and to attain effective treatment protocols.

Simple Summary: There are growing concerns about wildlife and livestock interactions and the impacts of those interactions on the sustainability of livestock. One of those concerns is the spillover of wildlife pathogens, including helminths, into livestock. This concern will likely become realized as the demand for free-range animal products increases. One such helminth with spillover potential is the eyeworm Oxyspirura petrowi. This eyeworm is common in many wild birds, and particularly common in Northern bobwhite quail. Related helminths are already commonly found in poultry raised in free-range conditions in developing nations. The purpose of this research was to investigate the lethality of fenbendazole, a widely available drug for treating parasites, to these eyeworms. The lethality estimates were similar to estimates of lethality to other roundworm parasites. However, studies that have investigated concentrations in host blood following administration of the drug indicate that it does not stay in the system long enough to achieve elimination of the parasite after a single dose. This indicates that in order to effectively treat eyeworm, fenbendazole must be delivered in a repeated or continuous manner. Oxyspirura petrowi is a heteroxenous nematode that infects the harderian gland and other ocular tissues in birds. High-intensity infections often cause damage to the infected tissues. Due to the nature of the infection sites, treatment of O. petrowi in these hosts can be difficult. Fenbendazole (FBZ) is a common anthelmintic used to treat birds for helminth infections; however, little information exists as to the efficacy of the drug on O. petrowi infections. The present study aims to estimate lethal concentrations of FBZ to O. petrowi. Adult O. petrowi were maintained in vitro and exposed to doses of 5, 50, 100, and 200 µM concentrations of FBZ and included both negative and vehicle controls. Exposure lasted 7.5 days and lethality was determined for each treatment. Negative and vehicle controls did not differ, and both had 75% survival at the end of the treatment period. The percentage survivorship in ascending order of concentration, corrected for the controls, was 66.67%, 44.44%, 33.33%, and 0%. LC10, LC50, and LC90 estimates were 7.5 ± 0.26, 49.1 ± 1.69, and 163.2 ± 5.63 µM, respectively. In the context of known pharmacokinetics of FBZ in birds, a single oral dose of FBZ can achieve exposure levels that are lethal to O. petrowi, but the drug does not stay in the system long enough. Thus, treatment of O. petrowi infections will require multiple oral doses over several days. [ABSTRACT FROM AUTHOR]

Continued advances in precision medicine rely on the widespread sharing of data that relate human genetic variation to disease. However, data sharing is severely limited by legal, regulatory, and ethical restrictions that safeguard patient privacy. Federated analysis addresses this problem by transferring the code to the data-providing the technical and legal capability to analyze the data within their secure home environment rather than transferring the data to another institution for analysis. This allows researchers to gain new insights from data that cannot be moved, while respecting patient privacy and the data stewards' legal obligations. Because federated analysis is a technical solution to the legal challenges inherent in data sharing, the technology and policy implications must be evaluated together. Here, we summarize the technical approaches to federated analysis and provide a legal analysis of their policy implications.

Abstract As an orally effective benzimidazole anthelmintic agent, fenbendazole was not only widely used in agriculture and animal husbandry to prevent and treat parasites, but also shows anti-cancer effects against several types of cancer, exhibits anti-cancer effects in paclitaxel and doxorubicin-resistant cancer cells. However, fenbendazole’s poor in water solubility (0.3 µg/mL), limits its clinical applications. Even great efforts were made toward increasing its water solubility, the results were not significant to reach anti-cancer drug delivery requirement (5–10 mg/mL). Through single factor and orthogonal strategy, many complex conditions were designed and used to prepare the complexes, the inclusion complex with methyl-β-cyclodextrin with 29.2 % of inclusion rate and 89.5% of inclusion yield can increase drug’s water solubility to 20.21 mg/mL, which is the best result so far. Its structure was confirmed by differential scanning calorimetry, scanning electron microscopic image, 1D and 2D NMR spectra in D2O. In its in vitro pharmacokinetic study, fenbendazole was 75% released in 15 min., in its in vivo pharmacokinetic study, the bio-availabilities of fenbendazole, its major metabolic anthelmintic agent oxfendazole and its minor metabolic anthelmintic agent oxfendazole were increased to 138%, 149% and 169% respectively, which would allow for fewer drug doses to achieve the same therapeutic effect and suggest that the complex can be used as a potential anticancer agent.

Abstract Fish are susceptible to blood-sucking parasite infections, which cause severe anemia, dyspnea, and ultimately death. However, veterinary drugs available for fish to treat such infectious diseases are lacking; thus, livestock drugs have been repurposed as aquatic animal drugs. Febantel (FBT) and fenbendazole (FBZ) are representative antiparasitic agents for livestock such as cattle, swine, and poultry, and are considered suitable as aquatic animal drugs. Therefore, we investigated the safety and efficacy of FBT and FBZ in fish and performed a risk assessment to determine the maximum residue limit in fish. Most studies indicate that FBT is rapidly converted to FBZ, which is metabolized to oxfendazole and oxfendazole sulfone. FBZ was frequently detectable in the plasma and tissues (e.g., muscle, skin, and the liver) in significant quantities than other metabolites. We regarded the liver as the target organ because reversible hepatocytic changes were observed in fish after administration of 100 mg/kg FBT for 9 days. No toxicological effects, such as increased mortality or decreased appetite, were observed when the fish were administered 50 mg/kg FBT for 3 days. The efficacy of the drugs was verified in various parasites, including H. heterocerca, H. okamotoi or Z. japonica, and M. seriolae, as causative agents of beko disease through laboratory and field trials. Although toxicity studies on FBZ in fish are limited, its safety has been demonstrated from toxicity studies in a wide range of animal models. The risk from using FBT and FBZ was negligible for human health because the ratio of the estimates of dietary exposure and acceptable daily intake was 78.4%.

The purpose of the research is to analyze the dynamics of fenbendazole (FBZ) and niclozamide (NZM) release from their solid dispersions (SD) of various compositions by dialysis through various semipermeable membranes in model systems that correspond to stomach and intestine environments. To evaluate the parasitocidal activity of experimental mixture compositions.Materials and methods. The study used substances of FBZ and NZM, and the polymer, polyvinylpyrrolidone (PVP). Mechanical processes were carried out in a LE-101 roller mill and an AGO-2 orbital centrifugal mill at different power density levels. The resulting SD of various compositions were studied for solubility. The dynamics of FBZ and NZM substance release from the SD were studied in a laboratory setup consisting of a temperature controlled glass with buffer solutions with pH = 9.18 (intestinal environment) and pH = 1.0 (stomach environment). The substance concentration in the dialysate was determined by HPLC and UV spectroscopy. The resulting complex SD of FBZ and NZM were studied for cestodocidal activity in a laboratory model of hymenolepiosis of white mice.Results and discussion. It was found that the substances release into a buffer solution with pH = 9.18 from the SD obtained in the roller mill is higher than that of the SD obtained in the AGO activator. The dialysis of the experimental compounds in a model system with a gastric juice medium observed only FBZ substance penetration through the membrane, which can be explained by protonation of the FBZ molecule which is a weak base. The NZM molecule, being a neutral molecule, does not penetrate through the semi-permeable partition into the hydrochloric acid environment; it remains entirely inside the dialysis bag. High anthelmintic efficacy rates (up to 100%) of SD complex FBZ : NZM : PVP obtained in the AGO activator and in the roller mill were recorded for the SD of composition 2 : 20 : 78 in the mice with hymenolepiosis. The activity of the base drug, the niclozamide substance, was 27.69%, which is 3 times lower than the activity of the resulting complex dispersions.

As an orally effective benzimidazole anthelmintic agent, fenbendazole was not only widely used in agriculture and animal husbandry to prevent and treat parasites, but also shows anti-cancer effects against several types of cancer, exhibits anti-cancer effects in paclitaxel and doxorubicin-resistant cancer cells. However, fenbendazole's poor in water solubility (0.3 µg/mL), limits its clinical applications. Even great efforts were made toward increasing its water solubility, the results were not significant to reach anti-cancer drug delivery requirement (5–10 mg/mL). Through single factor and orthogonal strategy, many complex conditions were designed and used to prepare the complexes, the inclusion complex with methyl-β-cyclodextrin with 29.2 % of inclusion rate and 89.5% of inclusion yield can increase drug's water solubility to 20.21 mg/mL, which is the best result so far. Its structure was confirmed by differential scanning calorimetry, scanning electron microscopic image, 1D and 2D NMR spectra in D2O. In its in vitro pharmacokinetic study, fenbendazole was 75% released in 15 min., in its in vivo pharmacokinetic study, the bio-availabilities of fenbendazole, its major metabolic anthelmintic agent oxfendazole and its minor metabolic anthelmintic agent oxfendazole were increased to 138%, 149% and 169% respectively, which would allow for fewer drug doses to achieve the same therapeutic effect and suggest that the complex can be used as a potential anticancer agent. [ABSTRACT FROM AUTHOR]

Fish are susceptible to blood-sucking parasite infections, which cause severe anemia, dyspnea, and ultimately death. However, veterinary drugs available for fish to treat such infectious diseases are lacking; thus, livestock drugs have been repurposed as aquatic animal drugs. Febantel (FBT) and fenbendazole (FBZ) are representative antiparasitic agents for livestock such as cattle, swine, and poultry, and are considered suitable as aquatic animal drugs. Therefore, we investigated the safety and efficacy of FBT and FBZ in fish and performed a risk assessment to determine the maximum residue limit in fish. Most studies indicate that FBT is rapidly converted to FBZ, which is metabolized to oxfendazole and oxfendazole sulfone. FBZ was frequently detectable in the plasma and tissues (e.g., muscle, skin, and the liver) in significant quantities than other metabolites. We regarded the liver as the target organ because reversible hepatocytic changes were observed in fish after administration of 100 mg/kg FBT for 9 days. No toxicological effects, such as increased mortality or decreased appetite, were observed when the fish were administered 50 mg/kg FBT for 3 days. The efficacy of the drugs was verified in various parasites, including H. heterocerca, H. okamotoi or Z. japonica, and M. seriolae, as causative agents of beko disease through laboratory and field trials. Although toxicity studies on FBZ in fish are limited, its safety has been demonstrated from toxicity studies in a wide range of animal models. The risk from using FBT and FBZ was negligible for human health because the ratio of the estimates of dietary exposure and acceptable daily intake was 78.4%. [ABSTRACT FROM AUTHOR]

Infection of Oxyuris spp., a gastrointestinal nematode, has been reported in reptiles around the world, including in the green iguana (Iguana iguana). In most cases, parasite control in reptiles relies on anthelmintics administration. Fenbendazole has been used as the drug of choice for parasite control in reptiles. However, the data of fenbendazole administration for Oxyuris spp. infection on green iguana (Iguana iguana) in Indonesia was absent. We evaluated the effect of fenbendazole administration (dose: 25 mg/kg body weight [BW] for five consecutive days per oral) for natural infection of Oxyuris spp. among thirty-three green iguanas in Malang Raya (Malang District, Malang City, and Batu City). The fecal examination was made through a modified Mc Master technique on the day-0, 7, 14, 21, and 31 post-treatment. The data on management (such as caging, feeding, and health program) conducted by the owners were recorded as well. The result showed that reduction of a hundred percent (100%) of egg per gram (epg) on day-31 post-treatment in all sampled animals. Iguanas were placed in individual and communal cages with daily cleaning and feeding. However, none of the owners arranged health programs such as anthelmintic treatment for their companion reptiles. This study can be used as a recommendation for future control of Oxyuris spp. in green iguanas in Indonesia. [ABSTRACT FROM AUTHOR]

Nematophagous fungi are a biological control tool used against gastrointestinal nematodes in livestock. These fungi prey on free-living larvae in faeces and could be affected by active drugs excreted post-treatment. This study aimed to determine in vitro and under environmental conditions the effect of the following anthelmintics on the fungus Duddingtonia flagrans: ivermectin, levamisole, albendazole, fenbendazole and ricobendazole. The in vitro effect of anthelmintics on fungal growth and predatory capacity was assessed in corn meal agar and coprocultures, respectively. Ivermectin (1, 2 and 10 ppm), fenbendazole (0.027, 0.054 and 1 ppm) and albendazole (1 ppm) significantly affected fungal development. The fungal efficacy against L3 was high in the control and levamisole coprocultures but decreased significantly in the presence of albendazole, fenbendazole, ricobendazole and ivermectin. The impact of levamisole on D. flagrans was further assessed under environmental conditions in autumn and winter; the fungal efficacy measured in faecal pats and the surrounding herbage was not affected by levamisole at any time. This study shows that using albendazole, fenbendazole, ricobendazole or ivermectin may compromise fungal activity, as these drugs affect the free-living stages of nematodes in faeces, but levamisole can be safely considered in parasite control strategies involving D. flagrans and anthelmintic treatments. [ABSTRACT FROM AUTHOR]

IntroductionPrescribing fenbendazole medicated feed for pheasants in the USA is considered extra-label drug use under CPG Sec 615.115, and a safe estimated withdrawal interval (WDI) must be applied following administration to this minor food-producing species. This study sought to determine the pharmacokinetic and residue depletion profile for fenbendazole and its major metabolites to estimate a WDI for pheasants following fenbendazole administration as an oral medicated feed.MethodPheasants (n = 32) were administered fenbendazole as an oral medicated feed (100 ppm) for 7 days. Fenbendazole, fenbendazole sulfoxide, and fenbendazole sulfone (FBZ-SO2) in liver and muscle samples were analyzed using HPLC-UV. Tissue WDIs were estimated using FDA, European Medicines Agency (EMA), and half-life multiplication methods for US poultry tolerances, EMA maximum residue limits, and the analytical limit of detection (LOD; 0.004 ppm). Terminal tissue elimination half-lives (T1/2) were estimated by non-compartmental analysis using a naïve pooled data approach.ResultsThe tissue T1/2 was 14.4 h for liver, 13.2 h for thigh muscle, and 14.1 h for pectoral muscle. The maximum estimated withdrawal interval was 153 h (7 days) for FBZ-SO2 in pectoral muscle using the FDA tolerance method (95% confidence interval for the 99th percentile of the population), and the LOD as the residue limit.DiscussionThe results from this study support the use of FBZ-SO2 as the marker residue in the liver of pheasants and the provision of evidence based WDIs following the extra-label administration of fenbendazole medicated feed (100 ppm) for 7 days.

Anthelmintic resistance has been reported in most goat-raising areas in India, yet little is known about the anthelmintic resistance status in gastrointestinal nematodes in goats in Rewa, Madhya Pradesh. The aim of this study was to determine the occurrence of anthelmintic resistance in goats in field conditions using Faecal Egg Count Reduction test (FECRT). 40 goats having egg per gram above 600 were divided into a control (G1) and three treatment groups (G2, G3 and G4) consisting of 10 goats in each group. Goats which were not given any treatment were kept as control group. Group G2, G3 and G4 goats were treated with fenbendazole @ 7.5 mg/kg BW orally, closantel @ 10 mg/kg BW orally and ivermectin @ 0.2 mg/kg BW subcutaneously, respectively. Percent reduction in faecal egg counts were monitored 14 days after treatment. The FECRT indicated percent reductions of 83, 94 and 94 for G2, G3 and G4, respectively. When analysed statistically using standard WAAVP protocol, anthelmintic resistance against fenbendazole and ivermectin was detected. These findings strongly suggest that anthelmintic resistance is a serious problem in strongyles in goats in Rewa and marked changes in gastrointestinal nematode management need to be instituted immediately to mitigate a worsening situation. [ABSTRACT FROM AUTHOR]

The substance fenbendazole is included in the composition of many anthelmintic drugs, in which the "chemical stability" parameter is one of the main characteristics when obtaining permission for the use of drugs in veterinary practice. Fenbendazole is characterized by low solubility in water and therefore the content of the substance is overestimated in its preparations, which increases the cost of the drug as well as the safety risks of pharmacotherapy. The possibilities of mechanochemical modification of fenbendazole were evaluated in order to improve the solubility index. During the mechanical processing treatment of the substance in the presence of polymeric substances, solid dispersions are formed, which have increased solubility and high anthelmintic activity. The inclusion in these dispersions of the third component, which is succinic acid, did not significantly change the solubility of fenbendazole. In all these dispersions, the substance remained unchanged both during the preparation of its solid dispersions and during their storage. When fenbendazole is modified in an organic solvent medium, the substance is partially converted into oxfendazole, which is one of its metabolites. The chemical stability of fenbendazole was confirmed via HPLC/MS and NMR spectroscopy. The anthelmintic activity of these compositions was evaluated and it was found that they have a high nematicidal activity. [ABSTRACT FROM AUTHOR]

BackgroundThe use of fenbendazole (FBZ) in terminal cancer patients has recently increased, as anthelminthic drugs, such as FBZ and benzimidazole, exhibit anti-tubulin effects in tumour cells.ObjectivesThe present study evaluated the in vitro anti-cancer effects of FBZ in five canine melanoma cell lines originating from the oral cavity (UCDK9M3, UCDK9M4, UCDK9M5, KMeC and LMeC).MethodsFive canine melanoma cell lines were treated with FBZ and analysed with cell viability assay, cell cycle analysis, western blot assay and immunofluorescence staining to identify apoptotic effect, cell cycle arrest, microtubule disruption and mitotic slippage.ResultsCell viability was reduced in all melanoma cell lines in a dose-dependent manner after FBZ treatment. Through cell cycle analysis, G2/M arrest and mitotic slippage were identified, which showed a time-dependent change. All treatment concentrations induced increased cleaved PARP signals in western blot analysis compared to the control groups. Immunofluorescence of cells treated for 24 h revealed defects in microtubule structure, multinucleation or macronucleation. With the exception of UCDK9M3, the melanoma cells showed mitotic slippage and post-slippage death, indicative of mitotic catastrophe.ConclusionsThese results indicate that FBZ exhibits anti-cancer effects in vitro against canine melanoma cells; however, further in vivo studies regarding the clinical applications of FBZ are required.

The substance fenbendazole is included in the composition of many anthelmintic drugs, in which the “chemical stability” parameter is one of the main characteristics when obtaining permission for the use of drugs in veterinary practice. Fenbendazole is characterized by low solubility in water and therefore the content of the substance is overestimated in its preparations, which increases the cost of the drug as well as the safety risks of pharmacotherapy. The possibilities of mechanochemical modification of fenbendazole were evaluated in order to improve the solubility index. During the mechanical processing treatment of the substance in the presence of polymeric substances, solid dispersions are formed, which have increased solubility and high anthelmintic activity. The inclusion in these dispersions of the third component, which is succinic acid, did not significantly change the solubility of fenbendazole. In all these dispersions, the substance remained unchanged both during the preparation of its solid dispersions and during their storage. When fenbendazole is modified in an organic solvent medium, the substance is partially converted into oxfendazole, which is one of its metabolites. The chemical stability of fenbendazole was confirmed via HPLC/MS and NMR spectroscopy. The anthelmintic activity of these compositions was evaluated and it was found that they have a high nematicidal activity.

Fenbendazole (FBZ) has been safely used as an antiparasitic agent in animals for decades, and the anticancer effects of FBZ have been studied through various mechanisms. However, there is a lack of in vivo studies that include lymphoma. Therefore, this study examined the effects of FBZ on EL-4 cells and a mouse T lymphoma model. FBZ induced G2/M phase arrest in EL-4 cells, resulting in cell death and decreased metabolic activity. However, FBZ had no anticancer effects on an EL-4 mouse lymphoma model in vivo, as evident by rapid weight loss and tumor growth comparable to the control. The FBZ-treated EL-4 cells expressed higher levels of PD-L1 and CD86, which are associated with T cell immunity in the tumor microenvironment (TME), than the controls. Furthermore, the hematoxylin and eosin staining of the FBZ-treated tumor tissues showed a starry sky pattern, which is seen in actively proliferating cancer tissues, and an immunohistochemical analysis revealed a high percentage of immunosuppressive M2 macrophages. These changes in the immune activity in the TME contradict the results of the in vitro experiments, and further studies are needed to determine the detailed mechanisms by which FBZ induces these responses.

The purpose of the research is to study the efficacy of a solid dispersion of fenbendazole at different stages of gastrointestinal nematodes of young sheep. Materials and methods. Evaluation of the efficacy of a solid dispersion of fenbendazole at different stages of gastrointestinal nematodes was carried out in the farms of the Samara region on 35 sheep aged 7–10 months naturally infected with gastrointestinal strongylates. Animals were divided into experimental and control groups of 8-9 animals each. A solid dispersion of fenbendazole was administered once orally at a dose of 2.0 mg/kg of active substance to the animals of the first experimental group. Animals of the 2nd group received the substance of fenbendazole at a dose of 2 mg/kg. The basic drug – Panakur was administered to the sheep of the 3rd experimental group at a dose of 5 mg/kg. Animals of the control group did not receive the drugs. The efficacy of the drugs was calculated in the experiment of «control test» based on the results of coproovoscopic examination, as well as on the results of helminthological necropsy of the digestive tract of animals, 3–5 sheep from each group. Results and discussion. The solid dispersion of fenbendazole showed 97.8–98.2% efficacy against adult strongylates and 80.6–87.5% against larvae. The substance of fenbendazole at the same dose – 2 mg/kg revealed 33.0–41.7% and 16.1–26.9% efficacy respectively. The basic drug Panakur showed 95.4–97.3% and 46.7–73.9% efficacy against imaginal strongylates and larvae respectively at a dose of 5.0 mg/kg of active substance.

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.

Oxyspirura petrowi is a heteroxenous nematode that infects the harderian gland and other ocular tissues in birds. High-intensity infections often cause damage to the infected tissues. Due to the nature of the infection sites, treatment of O. petrowi in these hosts can be difficult. Fenbendazole (FBZ) is a common anthelmintic used to treat birds for helminth infections; however, little information exists as to the efficacy of the drug on O. petrowi infections. The present study aims to estimate lethal concentrations of FBZ to O. petrowi. Adult O. petrowi were maintained in vitro and exposed to doses of 5, 50, 100, and 200 µM concentrations of FBZ and included both negative and vehicle controls. Exposure lasted 7.5 days and lethality was determined for each treatment. Negative and vehicle controls did not differ, and both had 75% survival at the end of the treatment period. The percentage survivorship in ascending order of concentration, corrected for the controls, was 66.67%, 44.44%, 33.33%, and 0%. LC10, LC50, and LC90 estimates were 7.5 ± 0.26, 49.1 ± 1.69, and 163.2 ± 5.63 µM, respectively. In the context of known pharmacokinetics of FBZ in birds, a single oral dose of FBZ can achieve exposure levels that are lethal to O. petrowi, but the drug does not stay in the system long enough. Thus, treatment of O. petrowi infections will require multiple oral doses over several days.

The present study was conducted on strongyle infected calves from organized and unorganized cattle farms located in and around Mhow (Indore, India) to assess the efficacy of polyherbal formulation (A mixture of Azadirchta indica, Momordica charantia, Allium cepa, Allium sativum, Brassica nigra, Musa paradisiaca, Cuminum cyminum, Curcuma longa and Piper nigrum) and fenbendazole. Total 12 infected calves (>500 EPG of strongyle) were randomly categorized in 2 groups of 6 calves in each. Group A was administered with polyherbal formulation, and Group B with fenbendazole. The anthelmintic efficacy of polyherbal formulation and fenbendazole was evaluated by faecal egg per gram (EPG) of strongyle and haemato-biochemical parameters. The pre-treatment mean EPG in both treated group were reduced significantly (p<0.05) on day 7, 14 and 21 post-treatment. Polyherbal formulation was found more effective against strongyle infection in comparison to fenbendazole. The values of Hb, PCV, TEC were increased significantly and TLC were decreased non-significantly in both polyherbal formulation and fenbendazole treated groups on day 21 post-treatment. Polyherbal formulation treated group showed significant decrease (p<0.05) in neutrophil, eosinophil count, whereas increased lymphocyte count. [ABSTRACT FROM AUTHOR]

Objective: Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models. Methods: EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC. Results: FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well. Conclusion: FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials. [ABSTRACT FROM AUTHOR]

The purpose of the research is to study the influence of various technological factors on obtaining of complex solid dispersions of anthelmintics with polyvinylpyrrolidone and licorice extract on anthelmintic efficacy in experimental trichinellosis of white mice.Materials and methods. The study of the nematodocidal activity of complex solid dispersions samples based on fenbendazole (FBZ), fenasal (FNS) and praziquantel (PZQ) with polyvinylpyrrolidone (PVP) and licorice extract (LE) obtained by mechanochemical technology at different ratios of components and different exposure times was carried out on 130 white mice experimentally infected with Trichinella spiralis in two experiments. On the 3rd day after infection, the animals were divided into experimental groups of 10 animals each. Samples of various complex solid dispersions of anthelmintics were administered intragastrically to the mice of the experimental groups at a dose of 2 mg/kg according to the active substance. FBZ substance was used as the basic drug at a dose of 2 mg/kg according to the active substance. Animals of the control groups did not receive the drugs. The animals were killed by decapitation on the 4th day after experimental drug samples administration, and the activity of the drugs was counted according to the results of helminthological necropsy of the intestine, the efficacy was calculated by the type of control test.Results and discussion. The efficacy of complex solid dispersions of FBZ and FNS with PVP polymer was higher in comparison with the activity of complexes with LE at the same duration of mechanochemical treatment in a roller mill. The FBZ activity decreased from 67.05 to 37.77% with a decrease in the duration of mechanochemical treatment from 24 h to 5 h and the efficacy of the FBZ : FNS complex with LE turned out to be almost at the level of the basic drug when treated for 1 h. The use of mechanochemical technology for obtaining of a solid dispersion of FBZ : FNS with PVP for targeted delivery makes it possible to increase the anthelmintic efficacy by 2.7 times compared with the activity of the FBZ substance, and with LE by 2.2 times. It was noted that complex solid dispersions of PBZ with PZQ have lower biological activity in comparison with compositions of FBZ with FNS.

The Northern Bobwhite (Colinus virginianus) is an economically important game bird within the Rolling Plains Ecoregion. Within this region, bobwhite is experiencing extreme cyclic population fluctuations which are resulting in a net decline in total population. It is suspected that within this region two helminth parasites, an eyeworm (Oxyspirura petrowi) and a cecal worm (Aulonocephalus pennula), are contributing to this phenomenon. However, this has been difficult to study as the primary mode of investigation would be the deployment of anthelmintic treatment. Unfortunately, no registered treatments for wild bobwhite currently exist. Thus, utilizing an anthelmintictreatment for wild bobwhite would require registration of that treatment with the U.S. Food and Drug Administration (FDA). As bobwhite are game birds that are hunted, they are considered food‐producing animals to the FDA, and as such require the assessment for the withdrawal of the drug residues to be assessed for human food safety. In this study, we optimized and validated a bioanalytical method for the quantification of fenbendazole sulfone in bobwhite following the U.S. FDA Center for Veterinary Medicine Guidance for Industry #208 [VICH GL 49 (R)] for assessment of fenbendazole sulfone drug residue in Northern bobwhite liver. The official method for quantifying fenbendazole sulfone in domestic chicken (Gallus gallus) was adapted for use in bobwhite. The validated method quantitation range is 2.5–30 ng/mL for fenbendazole with an average recovery of 89.9% in bobwhite liver. [ABSTRACT FROM AUTHOR]

Fenbendazole (FBZ), a benzymidazole (BZD) anthelmintic drug, is used for in-feed medication in pigs. BZD-containing drugs may induce cytochrome P450 isozymes (CYPs), particularly those members of the CYP1A subfamily. The current research evaluated the plasma and liver availability and metabolism of FBZ and its metabolites, oxfendazole (OFZ) and fenbendazole sulphone (FBZSO2), after the administration of the parent drug in feed, and characterized the effect of the sustained administration of the anthelmintic on the catalytic activities of xenobiotic metabolizing enzymes in pig liver. Five female Landrace piglets remained untreated (controls), and other six were treated with a pre-mix of FBZ, combined with feed, for 9 consecutive days as usually is recommended. Blood samples were collected from each treated animal up to day 9 and analyzed by HPLC; all animals were slaughtered for preparation of liver microsomes. Plasma concentration ratios OFZ/FBZ and FBZSO2/OFZ increased significantly (p < 0.05) from the beginning to the end of drug exposure, which may indicate an enhanced conversion of FBZ into its metabolites. FBZ represented 45.8 ± 3.4% of the total anthelmintic molecules in liver tissue. Increased CYP1A-dependent 7-ethoxy (24.5-fold, p = 0.0032) and 7-methoxyresorufin (17.2-fold, p = 0.0006) O-dealkylase activities was observed in liver microsomes from FBZ-treated animals. In addition, a 64% increase (p = 0.042) in the rate of FBZ S-oxidation was observed in pigs treated with the anthelmintic drug compared to that measured in untreated animals. Thus, the continuous FBZ administration may accelerate its own in vivo hepatic metabolism through the CYP1A pathway. [ABSTRACT FROM AUTHOR]

The study aimed to assess the effects of a therapeutic bath of five different antiparasitic drugs, in different baths and durations: fenbendazole (25 mg l-1, 12 h and 2 × 12 h), formaldehyde (0.17 ml l-1, 15 min), ivermectin (0.031 mg l-1, 1 h), mebendazole (1 mg l-1, 12 h) and levamisole (50 mg l-1, 2 h and 3 × 1 h) on the reduction on the intensity and prevalence of a monogenean infection (Dactylogyrus anchoratus) in juvenile carp. The best effect on reducing the parasite number was achieved with the bath in formaldehyde (0.17 ml l-1, 15 min) and fenbendazole (25 mg l-1, 2 × 12 h with 24 h break), where the infection was reduced by more than 90%. Registered veterinary medicinal products (VMPs) with the active substance of fenbendazole can successfully replace the use of unregistered formaldehyde in the treatment of monogenean infections.

The body of work described in this research paper evaluates the compatibility between Fenbendazole (Fen), which is a broad-spectrum anthelmintic with promising antitumor activity, and three polymeric excipients commonly applied in pharmaceutical dosage forms. The assessment of binary mixtures was performed by differential scanning calorimetry and thermogravimetric analysis/derivative thermogravimetry to predict physical and/or chemical interactions, followed by X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC) to confirm or exclude any interactions. Thermal studies suggested the presence of interactions between Fen and P 407, PCL, and PLA. To validate these data, XRD showed that Fen is compatible with PCL and PLA, suggesting some interaction with P 407. FTIR demonstrated that PCL and PLA can establish physical interactions with Fen; moreover, it suggested that P 407 interacts not only physically but also chemically, which was later proved by HPLC to be only new intermolecular interactions. This work supports the further application of P 407, PCL, and PLA for the development of new medicinal and veterinary formulations containing Fen, since they do not affect the physical and chemical characteristics of the active ingredient and consequently its bioavailability and therapeutic efficacy.

Fenbendazole (FZ) is a benzimidazole carbamate drug with broad-spectrum antiparasitic activity in humans and animals. The mechanism of action of FZ is associated with microtubular polymerization inhibition and glucose uptake blockade resulting in reduced glycogen stores and decreased ATP formation in the adult stages of susceptible parasites. A completely cured case of lung cancer became known globally and greatly influenced the cancer community in South Korea. Desperate Korean patients with cancer began self-administering FZ without their physician’s knowledge, which interfered with the outcome of the cancer treatment planned by their oncologists. On the basis of presented evidence, this review provides valuable information from PubMed, Naver, Google Scholar, and Social Network Services (SNS) on the effects of FZ in a broad range of preclinical studies on cancer. In addition, we suggest investigating the self-administration of products, including supplements, herbs, or bioactive compounds, by patients to circumvent waiting for long and costly FZ clinical trials.

The article deals about how study the control measures against ascariasis, which is widespread among birds in the western zone of the republic. The best effective drugs against helminthiasis of birds are fenbendazole, nilverm, mebednazol, fenesal, filixan, hyperazine. These drugs should be given with feed or as a solution in water, in the dosage and order according to their instructions. The research work was carried out in the "Chinarli" peasant farm located in Shamkir region, in the laboratory of the "Epizootology, microbiology and parasitology" department of the "Veterinary Medicine" faculty. Mattresses and feathers of birds should be neutralized by biothermal or thermal methods, buildings and equipment should be disinfected regularly, a disinfecting place should be made at the entrance of birdhouses, and the place of birds kept in camp conditions should be changed every year. If helminths adapt to one of these drugs, deworming should be replaced by another drug. [ABSTRACT FROM AUTHOR]

Fenbendazole (FBZ) is a broad-spectrum anthelmintic administered orally to ruminants; nevertheless, its poor water solubility has been the main limitation to reaching satisfactory and sustained levels at the site of the target parasites. Hence, the exploitation of hot-melt extrusion (HME) and micro-injection moulding (µIM) for the manufacturing of extended-release tablets of plasticised solid dispersions of poly(ethylene oxide) (PEO)/polycaprolactone (PCL) and FBZ was investigated due to their unique suitability for semi-continuous manufacturing of pharmaceutical oral solid dosage forms. High-performance liquid chromatography (HPLC) analysis demonstrated a consistent and uniform drug content in the tablets. Thermal analysis using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) suggested the amorphous state of the active ingredient, which was endorsed by powder X-ray diffraction spectroscopy (pXRD). Fourier transform infrared spectroscopy (FTIR) analysis did not display any new peak indicative of either a chemical interaction or degradation. Scanning electron microscopy (SEM) images showed smoother surfaces and broader pores as we increased the PCL content. Electron-dispersive X-ray spectroscopy (EDX) revealed that the drug was homogeneously distributed within the polymeric matrices. Drug release studies attested that all moulded tablets of amorphous solid dispersions improved the drug solubility, with the PEO/PCL blend–based matrices showing drug release by Korsmeyer–Peppas kinetics. Thus, HME coupled with µIM proved to be a promising approach towards a continuous automated manufacturing process for the production of oral solid dispersions of benzimidazole anthelmintics to grazing cattle. [ABSTRACT FROM AUTHOR]

Fenbendazole (FBZ) is a benzimidazole anthelmintic widely used to treat parasitic infections. The anticancer effect of FBZ has been recently highlighted leading to its consideration as a potential anticancer agent. Although previous studies have demonstrated the effect of FBZ on cancer cells, there is a paucity of studies on the effect of FBZ on lymphoma cells and normal immune cells. Herein, we investigated the effects of FBZ on a mouse lymphoma cell line, EL-4 cells, and spleen cells, using vincristine as a positive control. The cellular metabolic activity of EL-4 cells was decreased by FBZ, but that of the spleen cells was not decreased. Moreover, FBZ reduced the mitochondrial membrane potential and induced reactive oxygen species production in EL-4 cells, but not in spleen cells. FBZ induced G2/M phase arrest and increased the sub G0/G1 phase ratio, indicating apoptosis. Furthermore, compared to the control cells, the reactivity of spleen cells pretreated with FBZ to lipopolysaccharide was maintained. In summary, FBZ is cytotoxic to EL-4 cells, but not to spleen cells. This study provides experimental evidence that FBZ exerts an anticancer effect, and less cytotoxic effects and functional damage to normal spleen cells. [ABSTRACT FROM AUTHOR]

Fenbendazole (fen) or methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate is a broad-spectrum anthelmintic from the class of organic compounds known as benzimidazoles. Despite its pharmacological potential, fen has a limited application in oral pharmaceutical dosage forms due to its low aqueous solubility leading to an unsatisfactory bioavailability. This work aims to evaluate the compatibility between fen and poly(ethylene oxide) (PEO) applying differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), followed by the processing of solid dispersions using hot-melt extrusion (HME) with thermal evaluation by DSC, drug dispersion assessment by scanning electron microscopy (SEM) with electron-dispersive X-ray spectroscopy (EDX), and drug release profile by ultraviolet–visible spectroscopy (UV–Vis). The results obtained from the compatibility study using thermal and non-thermal techniques proved that fen and PEO are compatible. The thermal analysis of solid dispersions showed that the extrusion process increases the polymer's crystalline content when compared to powder mixtures. It also demonstrated that PEO dissolves fen crystalline structure, thus converting it to an amorphous state. SEM with EDX showed that solid dispersions had a homogeneous distribution of fen in the polymeric matrix with the presence of voids, pores, and ducts. Dissolution testing proved that solid dispersions of fen 5% and PEO 95% processed at 50 rpm was able to improve significantly the drug solubility in water-based media. Thus, this work brings a new solution to improving the poor-water solubility of fen using PEO to develop solid dispersion formulations processed by HME. [ABSTRACT FROM AUTHOR]

The present experiment was carried out to assess the comparative efficacy of ivermectin and fenbendazole individually for anthelmintic therapy for the hookworm infested dogs. Dogs presented to the Department of Veterinary Clinical Medicine or Veterinary Clinical Complex, Bhubaneswar were randomly screened for Ancylostoma caninum infection and the positive dogs were selected for the therapeutic trial Faecal samples were collected randomly from presented dogs immediately after defaecation or from the rectum directly using a faecal scoop. The collected sample was examined by floatation technique to detect the positive cases of Ancylostoma caninum infection. The dogs with normal clinical parameters and no eggs or ova in the faeces were included in in group 1 (n = 12). Dogs with faecal sample positive for Ancylostoma caninum ova were recruited for the comparative study (n = 24) which were grouped into two groups consisting of 12 dogs in each (group 2 and 3). Group 2 dogs (n = 12) were treated with ivermectin at 200 µg/kg body weight once orally repeated after 15 days with proper supportive therapy each time. Group 3 (n = 12) were treated with fenbendazole at 50 mg/kg body weight once orally repeated after 15 days with proper supportive therapy each time. Haematological examinations and serum biochemical tests were carried out in all groups each time on day 0, 15 and 30 of the experiment. The therapeutic efficacy of both the drugs was calculated on the basis of number of animals found free of Ancylostoma infection as determined by reduction in EPG count of the faeces of the group following the treatment. The reduction in eggs per gram (EPG) count on day 15 and day 30 was more significant in group 2 than group 3. The mean EPG count reduced significantly to 24.17 ± 11.44 on day 15 from day 0 level of 1650.00 ± 247.25 in fenbendazole-treated dogs. On day 30, the mean value further reduced to become nil.The 15th day after treatment, mean (± SE) value of protein, albumin and globulin was changed to 5.63 ± 0.12, 2.64 ± 0.12 and 2.99 ± 0.15 g/dl, respectively. The 30th day after treatment, the values were 6.23 ± 0.14, 3.20 ± 0.18 and 3.03 ± 0.21 g/dl, respectively. The total protein and albumin values were significantly changed from day 0 level in group 2 and 3 by 15th day and 30th day, respectively, at 1% level of significance. Following treatment with ivermectin, the 15th day haematological values increased significantly at 1% level (P < 0.01) of significance. There was significant increase in the values at 1% level on the 30th day compared to day 0 and the mean values were non-significantly comparable to the healthy control group except PCV and TEC. [ABSTRACT FROM AUTHOR]

The study aimed to assess the effects of a therapeutic bath of five different antiparasitic drugs, in different baths and durations: fenbendazole (25 mg l-1, 12 h and 2 × 12 h), formaldehyde (0.17 ml l-1, 15 min), ivermectin (0.031 mg l-1, 1 h), mebendazole (1 mg l-1, 12 h) and levamisole (50 mg l-1, 2 h and 3 × 1 h) on the reduction on the intensity and prevalence of a monogenean infection (Dactylogyrus anchoratus) in juvenile carp. The best effect on reducing the parasite number was achieved with the bath in formaldehyde (0.17 ml l-1, 15 min) and fenbendazole (25 mg l-1, 2 × 12 h with 24 h break), where the infection was reduced by more than 90%. Registered veterinary medicinal products (VMPs) with the active substance of fenbendazole can successfully replace the use of unregistered formaldehyde in the treatment of monogenean infections. [ABSTRACT FROM AUTHOR]

The body of work described in this research paper evaluates the compatibility between Fenbendazole (Fen), which is a broad-spectrum anthelmintic with promising antitumor activity, and three polymeric excipients commonly applied in pharmaceutical dosage forms. The assessment of binary mixtures was performed by differential scanning calorimetry and thermogravimetric analysis/derivative thermogravimetry to predict physical and/or chemical interactions, followed by X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC) to confirm or exclude any interactions. Thermal studies suggested the presence of interactions between Fen and P 407, PCL, and PLA. To validate these data, XRD showed that Fen is compatible with PCL and PLA, suggesting some interaction with P 407. FTIR demonstrated that PCL and PLA can establish physical interactions with Fen; moreover, it suggested that P 407 interacts not only physically but also chemically, which was later proved by HPLC to be only new intermolecular interactions. This work supports the further application of P 407, PCL, and PLA for the development of new medicinal and veterinary formulations containing Fen, since they do not affect the physical and chemical characteristics of the active ingredient and consequently its bioavailability and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Abstract Background The use of fenbendazole (FBZ) in terminal cancer patients has recently increased, as anthelminthic drugs, such as FBZ and benzimidazole, exhibit anti‐tubulin effects in tumour cells. Objectives The present study evaluated the in vitro anti‐cancer effects of FBZ in five canine melanoma cell lines originating from the oral cavity (UCDK9M3, UCDK9M4, UCDK9M5, KMeC and LMeC). Methods Five canine melanoma cell lines were treated with FBZ and analysed with cell viability assay, cell cycle analysis, western blot assay and immunofluorescence staining to identify apoptotic effect, cell cycle arrest, microtubule disruption and mitotic slippage. Results Cell viability was reduced in all melanoma cell lines in a dose‐dependent manner after FBZ treatment. Through cell cycle analysis, G2/M arrest and mitotic slippage were identified, which showed a time‐dependent change. All treatment concentrations induced increased cleaved PARP signals in western blot analysis compared to the control groups. Immunofluorescence of cells treated for 24 h revealed defects in microtubule structure, multinucleation or macronucleation. With the exception of UCDK9M3, the melanoma cells showed mitotic slippage and post‐slippage death, indicative of mitotic catastrophe. Conclusions These results indicate that FBZ exhibits anti‐cancer effects in vitro against canine melanoma cells; however, further in vivo studies regarding the clinical applications of FBZ are required.

Mixed gastrointestinal helminthoses, which combines Toxocara canis, Trichuris (T.) vulpis, Toxascaris leoninа, Uncinaria stenocephala, Ancylostoma caninum, and Dipylidium caninum in various combinations, are very common pets’ problems worldwide. It is unlikely necessary to choose between 100 % efficiency and for the patient’s body to heal the infected animals safely. The present work aims to develop an affordable scheme for adult dogs’ deworming, which will create a minimum load on the body due to the low drugs’ toxicity. Mixed breed dogs, 1—5 years old, representing both sexes, spontaneously infected with T. vulpis (100 % prevalence) in combination with other gastrointestinal helminths (from 12.7 to 45.1 %) were selected for study. Regimens combining Caniquantel® Plus (fenbendazole + praziquantel) and fenbendazole with a 24-hour interval were tested. After a single treatment of experimental animals with Caniquantel® Plus, no helminth eggs were detected in their faeces after three days, except for T. vulpis. Seven days after the start of the experiment, the intensity of infection of this nematode decreased by only 22.0 % (P < 0.001). Bodies and fragments of dead helminths were found in faeces 1—4 days after de-worming, with T. vulpis isolated only in 2 days in small quantities (4.54 ± 0.21 specimens per 100 g of faeces). Two-stage deworming with Caniquantel® Plus and fenbendazole after 24 hours resulted in 100 % efficiency against eggs of all parasites after five days. Helminths’ bodies stopped excreting after four days, and T. vulpis was detected within three days in substantive quantities (from 10.03 ± 0.45 to 36.8 ± 1.2 specimens per 100 g of faeces).

The purpose of the research is to study the embryotropic effect of supramolecular complex of fenbendazole (SMСF).Materials and methods. The experiment to assess the embryotropic properties of SMCF was carried out on 40 white female and 20 male rats in accordance with the Guidelines for the experimental (preclinical) study of new pharmacological substances. Pregnant female rats were divided into 3 experimental and one control groups. SMCF was administered intragastrically on the 1–6 days of embryogenesis (group 1); on the 7–14 days (group 2) and on the 15–19 days (group 3) in three times therapeutic dose – 6,0 mg/kg of active substance. The animals of the control group received saline from the first to the 19th days of pregnancy. Rats were euthanized on the 20th day of pregnancy. The uterus with fetuses was removed after laparotomy, the number of corpora lutea, implantation sites, the number of living, dead and resorbed fetuses were recorded, the weight and diameter of the placenta were determined. The embryos were examined, weighed, the craniocaudal sizes were determined, the levels of total embryonic, preimplantation and postimplantation embryo death were calculated. The fetuses were examined for abnormalities of internal organs and changes in the skeletal system according to the methods of J. G. Wilson (1965) and A. B. Dawson (1926), modified in the department of embryology of the IEM of the USSR Academy of Medical Sciences.Results and discussion. As a result, SMCF does not induce toxic effects on the fetus: mortality rates, size and weight of embryos were at the level of the control group in a threefold therapeutic dose 6,0 mg/kg at intragastric administration on the 1–6; 7–14 and 15–19 days of pregnancy. SMCF did not cause external and internal malformations.

Benzimidazole (BZ) drugs are frequently used to treat infections with the equine ascarid Parascaris univalens due to increasing resistance to macrocyclic lactones and pyrantel. Benzimidazole resistance is rare in ascarids in contrast to strongyle parasites where this resistance is widespread. In strongyles, single nucleotide polymorphisms (SNPs) at codons 167, 198 and 200 in a β-tubulin gene have been correlated to BZ resistance, but little is known about the β-tubulin genes and their possible involvement in BZ resistance in P. univalens and other ascarids. Previously two β-tubulin genes have been identified in P. univalens. In this study, we present five additional β-tubulin genes as well as the phylogenetic relationship of all seven genes to β-tubulins of other clade III and V nematodes. In addition, the efficacy of fenbendazole for treatment of P. univalens on a Swedish stud farm was studied in 2019 and 2020 using faecal egg count reduction test. Reductions varied from 73% to 88%, indicating the presence of a resistant P. univalens population on the farm. The emergence of BZ resistance emphasizes the need for development of molecular markers for rapid and more sensitive detection of resistant populations. We therefore investigated whether possible SNPs at positions 167, 198 or 200 in any of the β-tubulin genes could be used to distinguish between resistant and susceptible P. univalens populations. Amplicon sequencing covering the mutation sites 167, 198 and 200 in all seven β-tubulin genes revealed an absence of SNPs in both resistant and susceptible populations, suggesting that the mechanism behind BZ resistance in ascarids is different from that in strongyle nematodes and the search for a molecular marker for BZ resistance in P. univalens needs to continue.

The purpose of the research is to develop a methodology for the quantitative determination of fenbendazole (FBZ) and its metabolites in organs and tissues of sheep by high performance liquid chromatography tandem mass-spectrometry (HPLC-MS/MS).Materials and methods. The method for determining of FBZ and its metabolites after the administration of the supramolecular complex of fenbendazole was validated in accordance with international guidelines for the following indicators: linearity, recovery, specificity, precision, accuracy, limits of quantitative and qualitative determination.Results and discussion. The method of quantitative analysis of FBZ and its metabolites sulfone and sulfoxide in the body of sheep after the administration of the supramolecular complex has been adapted. The proposed method has a linear relationship (R > 0.99) in the range of 5–1000 ng / g and has shown a good reproducibility and accuracy.

The purpose of the research is developing a methodology for application of the supramolecular complex of fenbendazole (SMCF) against helminthosis in ruminants.The SMCF was obtained by the method of mechanochemical technology with polyvinylpyrrolidone (PVP) in a ratio of 1 : 10 in a balling drum. The drug was produced in plastic cans of 2, 4 and 8 kg and stored in its original packaging in dry, nonresidential area. The SMCF was used against gastrointestinal strongylatosis, dictyocaulosis and monieziosis of sheep and goats at a dose of 20 mg/kg (2 mg/kg for the active substance). The methodology provides a brief chemical characteristic of the SMCF, summarizes its mode of action, and describes toxicological properties, which gives an idea of the drug in general. The procedure is described for preparing the drug for use on animals, both individually and in a group. Reasoned recommendations are given on the timing for animal slaughter, and the use of milk after treating cows.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease with unknown etiology. Despite substantial progress in understanding the pathogenesis of pulmonary fibrosis and drug development, there is still no cure for this devastating disease. Fenbendazole (FBZ) is a benzimidazole compound that is widely used as an anthelmintic agent and recent studies have expanded the scope of its pharmacological effects and application prospect. This study demonstrated that FBZ treatment blunted bleomycin-induced lung fibrosis in mice. In vitro studies showed that FBZ inhibited the proliferation and migration of human embryo lung fibroblasts. Further studies showed that FBZ significantly inhibited glucose consumption, moderated glycolytic metabolism in fibroblasts, thus activated adenosine monophosphate-activated protein kinase (AMPK), and reduced the activation of the mammalian target of rapamycin (mTOR) pathway, thereby inhibiting transforming growth factor-β (TGF-β1)-induced fibroblast-to-myofibroblast differentiation and collagen synthesis. In summary, our data suggested that FBZ has potential as a novel treatment for pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background: Korean society has faced challenges in communicating with cancer patients about false information related to complementary alternative medicine. As the situation has become severewith the 2020 fenbendazole scandal, the demand for reliable information from health authorities has increased. Objectives: This study aimed to examine patients' acquisition patterns and perception of false information by presenting empirical evidence to help health authorities enable effective preemptive responses in the cancer communication context. Method: We conducted a focus group interview with 21 lung cancer patients who were informed about fenbendazole based on a semi-structured questionnaire with three categories: 1) acquisition channel of the general cancer information and the false information, 2) quality of obtained information, and 3) perception toward it. The interviewees, comprising 13 men and eight women, were aged 50 or older. Participants' current stages of cancer were stages one, three, and four and there were seven people in each stage. Results: 1) Acquisition channel: Participants had their first encounter with false information through the TV, while the channels to obtain general cancer information were through Internet communities or portal sites. YouTube was a second channel to actively search for information regardless of the information type. 2) Information quality: participants had only fragmented information through media. 3) Perception: Most patients had a negative attitude toward complementary and alternative medicine information such as fenbendazole. They perceive that it needs to be verified by experts and filtered according to their arbitrary criteria. They had vague expectations based on a hope for "what if" at the same time. Conclusions: Despite the complex media environment, traditional or legacy media is an important channel to encounter information. YouTube is independent of other media as an "active" information-seeking channel. Patients required the appropriate intervention of experts and governments because they perceived that they had obtained irrational and unreliable information from the media. Suggestions are made about how health authorities can construct an effective communication system focusing on the user to prevent patients from getting false cancer information. [ABSTRACT FROM AUTHOR]