Fenbendazole Research Articles

Medication with fenbendazole in feed: plasma concentrations and effects on hepatic xenobiotic metabolizing enzymes in swine.

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.

Fenbendazole Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice via Suppression of Fibroblast-to-Myofibroblast Differentiation.

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.

Untargeted metabolomics-assisted comparative cytochrome P450-dependent metabolism of fenbendazole in human and dog liver microsomes

Fenbendazole (FBZ), a benzimidazole carbamate anthelmintic, has attracted attention for its antitumor activity. This study examined the metabolic characteristics of FBZ in humans compared with those in dogs. The phase I metabolites were identified in liver microsomal incubates using liquid chromatography–mass spectrometry (MS)-based untargeted metabolomics approaches. Seven metabolites of FBZ were identified by principal component analysis and orthogonal partial least square-discriminant analysis based on the global ion variables of the FBZ incubation groups. The chemical structure of the FBZ metabolites was suggested by examining the MS/MS spectrum and isotope distribution pattern. Cytochrome P450 (CYP) 1A1, CYP2D6, and CYP2J2 were the major isozymes responsible for the FBZ metabolism. No differences in the types of metabolites produced by the two species were noted. Multivariate analysis of human and dog incubation groups showed that five metabolites were relatively abundant in humans and the other two were not. In summary, the phase I metabolic profile of FBZ and the comparative metabolism between humans and dogs were examined using an untargeted metabolomics approach. This study suggests a successful investigation of FBZ metabolism in humans for conducting safety assessments regarding drug repositioning.

Fenbendazole resistance in Heterakis gallinarum, the vector of Histomonas meleagridis, on a broiler breeder farm in South Carolina.

Parasites are highly prevalent in poultry; thus, the management of parasites is a key component in the profitable production of poultry. The most common nematode parasite of poultry, Heterakis gallinarum, typically causes no direct pathology but is the vector of Histomonas meleagridis, a highly pathogenic protozoan parasite that causes blackhead disease. There are no approved treatments for H. meleagridis, making control reliant on controlling the helminth vector. In the United States, the benzimidazole anthelmintic fenbendazole (FBZ) is the only approved treatment for H. gallinarum. We were contacted by an industry veterinarian regarding clinical problems with histomoniasis despite frequent anthelmintic treatments. Given that we had recently diagnosed FBZ resistance in the closely related parasite Ascaridia dissimilis, we were interested to determine if H. gallinarum had also evolved resistance. An initial on-farm pilot study using 20 birds suggested that FBZ was poorly effective, therefore a larger controlled study was initiated. Heterakis gallinarum eggs were isolated from litter at the farm and used to infect 118 chicks. Treatment groups included a non-treated control, a label-, and a 2×-label dose of FBZ, with 36 birds per group divided into two replicates of 18 birds. Three weeks post-hatch, birds were infected with 150 embryonated eggs. Two weeks post-infection treated birds were administered either a label- or 2× label-dose of FBZ in water for five days (SafeGuard® Aquasol, 1mg/kg BW). To increase the likelihood that all birds consumed the full intended dose, the dosage was calculated using 1.25 times the average body weight. One-week post-treatment, birds were euthanized, and parasites enumerated. There were no significant differences in worm numbers recovered from any of the three groups (p-value=0.3426), indicating that both dosages of FBZ failed to provide the expected levels of efficacy. These data provide strong evidence that H. gallinarum has developed resistance to FBZ on this farm. Consequently, on this farm, or any farm with FBZ-resistant H. gallinarum, H. meleagridis will continue to cycle in an unrestricted manner despite administration of anthelmintic treatments. Given recent evidence of increasing problems with histomoniasis, and the fact that resistance was documented on the first farm we investigated, further investigations are needed to determine the prevalence of resistance in H. gallinarum on poultry farms. These data, when viewed together with our recent findings of FBZ resistance in A. dissimilis on multiple farms, suggest that drug resistance in ascarid nematodes may be an emerging problem in the US poultry industry.

Exceptional Repositioning of Dog Dewormer: Fenbendazole Fever.

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.

Anthelmintic resistance of horse strongyle nematodes to fenbendazole in Lithuania

BackgroundControl of strongyle infections presents a global challenge for horse practitioners due to the development of anthelmintic resistance (AR), however comprehensive information on AR in Lithuania is still lacking. The aim of this study was to assess the current situation of fenbendazole (FBZ) AR in horses at stable level in Lithuania.ResultsFaecal samples from 121 horses from six stables were examined using the Mini-FLOTAC method. Of these, 89 horses met the inclusion criteria that included strongyle faecal egg counts (FEC) exceeding 200 eggs per gram (EPG). Faecal egg count reduction tests (FECRTs) were performed in these. AR was evaluated at horse stable level based on faecal egg count reduction (FECR) and the lower limit of the 95% credible interval (LLCI) using the Bayesian hierarchical model. This study confirmed that strongylids (Cyathostominae (CYA)) resistant to FBZ are pervasive in Lithuania. FBZ was ineffective in three of the six stables (FECR 77.1–79.0%; 49.8–99.8 LLCI), was suspected to be ineffective in one stable (FECR 93.6%; 85.4–100 LLCI) and was effective (FECR 99.8–100%; 99.8–100 LLCI) in two stables. FEC showed a significant (P < 0.01) difference between the treatment and control groups. Only CYA larvae were detected in larval cultures derived from strongyle-positive faecal samples collected 14 days after treatment of a test group with FBZ.ConclusionThis in vivo study showed that resistance to FBZ in the treatment of strongyle nematodes is prevalent in horse stables in Lithuania. These findings should guide the implementation of more sustainable management of strongyle infections in horses in Lithuania.

Worm control practices on free-range egg farms in Australia and anthelmintic efficacy against nematodes in naturally infected layer chickens.

This study investigated worm control practices by free-range egg farmers and the efficacy of the commercial anthelmintics levamisole (LEV), piperazine (PIP), flubendazole (FLBZ) and fenbendazole (FBZ) against gastrointestinal nematodes on two free-range layer farms in Australia. An online survey comprising 36 questions was designed and implemented using SurveyMonkey. The survey contained questions about participant demographics, farm and flock characteristics, perceived intestinal worm importance, infection monitoring, deworming and other worm control practices. A link for the survey was emailed to free range egg producers from their industry body in December 2019. The anthelmintic efficacy trial was conducted in a total of 229 layers naturally infected with Ascaridia galli, Hetarakis gallinarum, Capillaria spp. and/or tape worms. Chickens received a single oral dose of LEV (28mg/kg), PIP (100mg/kg), FBZ (10mg/kg) or LEV-PIP co-administered at their full individual doses, and FLBZ (Flubenol®), 30ppm or 60ppm) in the feed over 7days. Anthelmintic efficacies were estimated by both worm count reduction (WCR %) and excreta egg count reduction (EECR %) tests 10days after start of treatment. The survey with a response rate of 16/203, revealed that worm infection was of moderate concern to the producers and the majority (68%) felt that the current anthelmintics work effectively. The level of understanding of worms, monitoring and control practices did not reveal any major deficiencies of concern. The most commonly used anthelmintic was LEV (73%) followed by PIP (45%). Based on a standard cut-off value (≥90%), LEV, LEV-PIP, and FBZ attained the desired efficacy but PIP exhibited reduced efficacy against immature A. galli (61-85%), all stages of H. gallinarum (42-77%) and Capillaria spp. (25-44%). FLBZ was highly effective against all stages of roundworms and tapeworm infections. Even though there was some association between the efficacies estimated by WCR % and EECR % the latter was poorly associated in the natural infection model and hence does not provide a reasonable alternative for assessing anthelmintic efficacy when immature stages of the lifecycle are included. These results show no evidence of loss of susceptibility to the tested anthelmintics on these farms supporting the perception of producers that participated in the survey that current treatments work effectively. The reduced efficacy of PIP against some species and immature stages is related to its spectrum of activity rather than providing evidence of emerging resistance.

β-Lactoglobulin-Modified Mesoporous Silica Nanoparticles: A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostate Cancer Cells.

The clinical utilization of fenbendazole (FBZ) as a potential anticancer drug has been limited due to its low water solubility, which causes its low bioavailability. The development of a drug nanoformulation that includes the solubilizing agent as a drug carrier can improve solubility and bioavailability. In this study, Mobil Composition of Matter Number 48 (MCM-48) nanoparticles were synthesized and functionalized with succinylated β-lactoglobulin (BLG) to prevent early-burst drug release. The BLG-modified amine-functionalized MCM-48 (MCM-BLG) nanoparticles were loaded with FBZ to produce the drug nanoformulation (FBZ-MCM-BLG) and improved the water solubility and, consequently, its anticancer effects against human prostate cancer PC-3 cells. The prepared FBZ-MCM-BLG was characterized in terms of size, zeta potential, drug loading capacity, morphology, thermal and chemical analyses, drug release, cellular uptake, cell viability, cell proliferation, production of reactive oxygen species (ROS), and cell migration. The results demonstrated that the FBZ-MCM-BLG nanoparticles have a spherical morphology with a size and zeta potential of 369 ± 28 nm and 28 ± 0.4 mV, respectively. The drug loading efficiency of the new nanoformulation was 19%. The release of FBZ was pH-dependent; a maximum cumulative release of about 76 and 62% in 12 h and a burst release of 53 and 38% in the first 0.5 h was observed at pH 1.2 and 6.8, respectively. The prepared FBZ-MCM-BLG formulation demonstrated higher cytotoxicity effects against PC-3 cells by 5.6- and 1.8-fold, respectively, when compared to FBZ and FBZ-MCM nanoparticles. The new formulation also increased the production of ROS by 1.6- and 1.2-fold and inhibited the migration of PC-3 cells when compared to the FBZ and FBZ-MCM nanoparticles, respectively. Overall, FBZ-MCM-BLG nanoparticles improved FBZ delivery to PC-3 cells and have the potential to be evaluated for the treatment of prostate cancer following a comprehensive in vivo study.

G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells.

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.

Evaluation of in vitro methods of anthelmintic efficacy testing against Ascaridia galli.

To investigate methods for in vitro assessment of anthelmintic efficacy against the chicken nematode Ascaridia galli this study firstly evaluated sample preparation methods including recovery of eggs from excreta using different flotation fluids and induced larval hatching by the deshelling-centrifugation method and the glass-bead method with or without bile. It then evaluated two in vitro assays, the in-ovo larval development assay (LDA) and larval migration inhibition assay (LMIA), for anthelmintic efficacy testing against A. galli using fresh eggs and artificially hatched larvae, respectively. Four anthelmintics, thiabendazole (TBZ), fenbendazole (FBZ), levamisole (LEV) and piperazine (PIP) were employed using an A. galli isolate of known susceptibility. The results suggested that the LDA and LMIA could successfully be used to generate concentration response curves for the tested drugs. The LDA provided EC50 values for inhibition of egg embryonation of 0.084 and 0.071 μg/ml for TBZ and FBZ, respectively. In the LMIA, the values of effective concentration (EC50) of TBZ, FBZ, LEV and PIP were 105.9, 6.32, 349.9 and 6.78 × 107 nM, respectively. For such in vitro studies, a saturated sugar solution showed high egg recovery efficiency (67.8%) and yielded eggs of the highest morphological quality (98.1%) and subsequent developmental ability (93.3%). The larval hatching assays evaluated did not differ in hatching efficiency but the deshelling-centrifugation method yielded larvae that had slightly better survival rates. For final standardization of these tests and establishment of EC50 reference values, tests using isolates of A. galli of defined resistance status need to be performed.

Methodology for the quantitative determination of fenbendazole and its metabolites in organs and tissues of animals by high performance liquid chromatography with tandem mass spectrometry detection

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 &gt; 0.99) in the range of 5–1000 ng / g and has shown a good reproducibility and accuracy.

Improving the in vitro dissolution rate and pharmacokinetic performance of fenbendazole in sheep using drug nanocrystals

Benzimidazole methylcarbamate anthelmintics, including fenbendazole (FBZ), have only limited water solubility and small differences in drug solubility may have a major influence on their absorption, pharmacokinetic behavior and anthelmintic efficacy. To improve FBZ water solubility and dissolution rate, novel self-dispersible nanocrystals (SDNCs) of FBZ were recently described. In this work, the pharmacokinetic behavior of the SDNCs of FBZ and Poloxamer 188 was compared against a physical mixture (PM) of its components. The experiment was conducted following a crossover design with two different experimental phases. In phase I, sheep were treated with the SDNC (n = 3) or the PM (n = 3) formulations by the intraruminal route at the same dose rate (5 mg/kg). The treatment groups were reversed after a 7-days washout period. A non-compartmental analysis of the concentration in plasma versus time results showed that the calculated Cmax and AUC0-T were significantly higher (p < 0.05) for FBZ and its metabolites after the SDNC treatment compared to the PM (for FBZ: Cmax 0.346 μg/mL and AUC0-T 10.1 μg.h/mL after the SDNC vs Cmax 0.157 μg/mL and AUC0-T 5.1 μg.h/mL after the PM treatment). Additionally, population pharmacokinetic parameters of FBZ were estimated for the first time in sheep. In conclusion, the formulation of FBZ as SDNCs is a promising approach to improve FBZ dissolution reaching a higher drug plasma exposure in ruminants.

PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells.

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.

Inhibitory effects of fenbendazole, an anthelmintics, on lipopolysaccharide-activated mouse bone marrow cells

Fenbendazole (FBZ) is a commonly used anthelmintic in veterinary medicine that has recently been found to have anticancer effects in humans. On the other hand, few studies have examined the anti-inflammatory effects of FBZ, and its mechanism is unknown. In this study, mouse bone marrow cells (BMs) were treated with lipopolysaccharide (LPS), a representative inflammation-inducing substance, to generate a situation similar to osteomyelitis in vitro. The effect of FBZ on inflammatory BMs was examined by measuring the metabolic activity, surface marker expression, cell nuclear morphology, and mitochondrial membrane potential (MMP) of BMs. FBZ decreased the metabolic activity and MMP of LPS-treated BMs. Annexin Ⅴ-fluorescein isothiocyanate/propidium iodide staining and Hoechst 33342 staining showed that FBZ reduced the number of viable cells and induced the cell death of inflammatory BMs. In addition, FBZ reduced the proportion of granulocytes more than B lymphocytes in LPS-treated BMs. Overall, FBZ induces cell death by destabilizing the MMP of LPS-induced inflammatory BMs. FBZ can play a role as an anthelmintic and anticancer agent and an anti-inflammatory agent.

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.

Optimization and Pharmacokinetic Evaluation of Synergistic Fenbendazole and Rapamycin Co-Encapsulated in Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles

PurposeWe aimed to develop a nanocarrier formulation incorporating fenbendazole (FEN) and rapamycin (RAPA) with strong efficacy against A549 cancer cells. As FEN and RAPA are poorly soluble in water, it is difficult to apply them clinically in vivo. Therefore, we attempted to resolve this problem by encapsulating these drugs in polymeric micelles.MethodsWe evaluated drug synergy using the combination index (CI) values of various molar ratios of FEN and RAPA. We formed and tested micelles composed of different polymers. Moreover, we conducted cytotoxicity, stability, release, pharmacokinetic, and biodistribution studies to investigate the antitumor effects of FEN/RAPA-loaded mPEG-b-PCL micelles.ResultsWe selected mPEG-b-PCL-containing FEN and RAPA at a molar ratio of 1:2 because these particles were consistent in size and had high encapsulation efficiency (EE, %) and drug loading (DL, %) capacity. The in vitro cytotoxicity was assessed for various FEN, RAPA, and combined FEN/RAPA formulations. After long-term exposures, both the solutions and the micelles had similar efficacy against A549 cancer cells. The in vivo pharmacokinetic study revealed that FEN/RAPA-loaded mPEG-b-PCL micelles had a relatively higher area under the plasma concentration–time curve from 0 to 2 h (AUC0–2 h) and 0 to 8 h (AUC0–8 h) and plasma concentration at time zero (Co) than that of the FEN/RAPA solution. The in vivo biodistribution assay revealed that the IV injection of FEN/RAPA-loaded mPEG-b-PCL micelles resulted in lower pulmonary FEN concentration than the IV injection of the FEN/RAPA solution.ConclusionWhen FEN and RAPA had a 1:2 molar ratio, they showed synergism. Additionally, using data from in vitro cytotoxicity, synergism between a 1:2 molar ratio of FEN and RAPA was observed in the micelle formulation. The FEN/RAPA-loaded mPEG-b-PCL micelle had enhanced bioavailability than the FEN/RAPA solution.

Comparative therapeutic efficacies of oral and in-water administered levamisole, piperazine and fenbendazole against experimental Ascaridia galli infection in chickens

Evidence on the current efficacy status of anthelmintics used in the Australian poultry sector is lacking. A controlled trial was conducted to evaluate the efficacy of three commonly used anthelmintics, namely levamisole (LEV), piperazine (PIP) and fenbendazole (FBZ) plus levamisole-piperazine combination (LEV-PIP) against a field strain of A. galli recovered following flock treatment with LEV. A total of 108 A. galli infected cockerels were randomized into nine experimental groups of 12 cockerels each (eight treatments and one untreated control) with each treatment administered by two routes (oral drench or in drinking water). Chickens received label-recommended doses of LEV (28 mg/kg) and PIP (100 mg/kg) while LEV-PIP involved both compounds co-administered at their full individual dose rates. FBZ was tested at two dose rates; 10 mg/kg as a single oral drench or 5 mg/kg in drinking water over 5 days. Anthelmintic efficacies were assessed by worm count reduction (WCR%) and excreta egg count reduction (EECR%) estimated by two methods. Ten days post treatment, the untreated control birds harboured significantly higher worm counts (P < 0.0001) than those in all treatment groups irrespective of the mode drug of application. Oral drenching caused a greater reduction in worm and egg counts (P < 0.05) than medication in drinking water. Based on geometric worm counts the percentage efficacies for the oral drench were 99.1, 96.3, 97.2 and 100 % respectively for LEV, PIP, FBZ and LEV-PIP, and for administration in water 96.4, 93.7, 88.7 and 97.7 % respectively. Efficacies based on EECR% were consistent with WCR% with strong positive linear association between efficacy values. In conclusion, our results demonstrate no evidence of loss of susceptiblity of the test A. galli isolate to both LEV and PIP contrary to our hypothesis. Additional efficacy studies are needed using A. galli isolates sourced from different poultry flocks across Australia.

In‐feed trials of fenbendazole and other chemical/natural compounds against Sparicotyle chrysophrii (Monogenea) infections in Sparus aurata (Osteichthyes)

In‐feed trials of fenbendazole and other chemical/natural compounds against <i>Sparicotyle</i> <i> </i> <i>chrysophrii</i> (Monogenea) infections in <i>Sparus</i> <i> </i> <i>aurata</i> (Osteichthyes)

Soybean (Glycine max) Is Able to Absorb, Metabolize and Accumulate Fenbendazole in All Organs Including Beans.

Although manure is an important source of minerals and organic compounds it represents a certain risk of spreading the veterinary drugs in the farmland and their permeation to human food. We tested the uptake of the anthelmintic drug fenbendazole (FBZ) by soybean, a common crop plant, from the soil and its biotransformation and accumulation in different soybean organs, including beans. Soybeans were cultivated in vitro or grown in a greenhouse in pots. FBZ was extensively metabolized in roots of in vitro seedlings, where sixteen metabolites were identified, and less in leaves, where only two metabolites were found. The soybeans in greenhouse absorbed FBZ by roots and translocated it to the leaves, pods, and beans. In roots, leaves, and pods two metabolites were identified. In beans, FBZ and one metabolite was found. FBZ exposure did not affect the plant fitness or yield, but reduced activities of some antioxidant enzymes and isoflavonoids content in the beans. In conclusion, manure or biosolids containing FBZ and its metabolites represent a significant risk of these pharmaceuticals entering food consumed by humans or animal feed. In addition, the presence of these drugs in plants can affect plant metabolism, including the production of isoflavonoids.

146 Fecal egg count reduction in juvenile and mature horses administered fenbendazole or moxidectin/praziquantel dewormer

Parasite resistance is a concern in horses and can be monitored by performing fecal egg counts (FECs). Unfortunately, FECs are not performed regularly, which could contribute to developing anthelmintic resistance as it may lead to deworming too frequently or not using an effective dewormer for the horse. This study aims to evaluate the ability of pellet and paste fenbendazole (FBZ) and a paste moxidectin/praziquantel (MOX/PZQ) dewormer to reduce parasite populations in juvenile and mature horses in River Falls, Wisconsin. To evaluate dewormers, horses with an initial FEC ≥50 eggs per gram (EPG) were used. For FBZ, horses were blocked by shedding level as low (<200 EPG), moderate (200 – 500 EPG), and high (>500 EPG) shedders and assigned to the pellet (n = 21) or paste (n = 23) FBZ treatment. Two-weeks post-treatment, another FEC was taken and a fecal egg count reduction (FECR) was calculated. Eight-weeks following this study, another FEC was performed and horses with ≥50 EPG were administered a MOX/PZQ paste (n = 46). Two-weeks post-treatment, another FEC was taken and subsequent FECR was calculated. Results from this study indicated no differences were observed for horses receiving pellet or paste FBZ with a FECR of 57.4% and 65.7%, respectively ( P ≥ 0.05). Additionally, no difference in the FECR for juvenile versus mature horses or shedding level was observed regardless of the dewormer used ( P ≥ 0.05). While both FBZ and MOX/PZQ reduced FECs when comparing the pre- and post-treatment EPG ( P ≤ 0.01), the average FECR was 60.4% and 98.5% for horses receiving FBZ and MOX/PZQ, respectively. These results demonstrate parasite resistance to FBZ was observed in this herd while MOX/PZQ was still effective in reducing FECs.