Fenbendazole Administration Research Articles

Estimation of withdrawal interval recommendations following administration of fenbendazole medicated feed to ring-necked pheasants (Phasianus colchicus).

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. 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. 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. 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.

Benzimidazole‐associated pancytopenia in a dog with presumed Heterobilharzia americana infection

AbstractAdverse drug events are classified into type A (dose‐dependent and common) or type B (idiosyncratic and uncommon) reactions. Benzimidazole toxicosis in veterinary medicine typically induces nonspecific signs such as gastrointestinal distress and infrequent myelosuppression. Pancytopenia from benzimidazoles is exceptionally rare, with only one reported case. We present a 12‐year‐old, female, spayed, mixed‐breed dog with acute lethargy, anorexia, pyrexia and severe leukopenia after high‐dose benzimidazole therapy for suspected liver fluke infection. Despite hospitalisation, the dog remained unresponsive to antimicrobial therapies, developed neutropenic sepsis and was euthanized. Bone marrow analysis indicated marked haematopoietic hypoplasia suggestive of a type A adverse drug event secondary to an incidental, high‐dose fenbendazole administration.

Pneumothorax in a persistent canine Angiostrongylus vasorum infection.

Canine angiostrongylosis is a gastropod-borne parasitosis caused by the cosmopolitan nematode Angiostrongylus vasorum. It is associated with cardiorespiratory disorders and eventually fatal coagulopathies. A 6-months-old female dog previously diagnosed with bronchopneumonia and pneumothorax, treated accordingly without success, was hospitalized for further treatment. Complementary diagnostics confirmed previous findings plus pneumomediastinum, thoracic exudate, leucocytosis, thrombocytosis, hypercoagulability, and hyperglobulinemia. Coprological analysis showed a severe patent A. vasorum infection. After the third daily fenbendazole administration, all A. vasorum larvae were found dead in follow-up coprological analyses while in intensive care. Upon release, the dog was monitored until full clinical recovery 3months later. Up to date, A. vasorum infection-related pneumothorax was rarely described, particularly with full recovery of such a young patient. Thus, a parasitological aetiology should be considered for dogs with severe bronchopneumonia or pneumothorax, especially in Europe and South America where increasing numbers of canine angiostrongylosis cases call for enhanced awareness of veterinary practitioners.

Evaluation of the effects of anthelmintic administration on the fecal microbiome of healthy dogs with and without subclinical Giardiaspp. and Cryptosporidium canisinfections.

BackgroundThe gastrointestinal microbiome plays an important role in host health and there is increasing concern regarding the deleterious effects of pharmaceuticals on the fecal microbiome. The effect of anthelmintic therapy on the fecal microbiome in dogs has not yet been evaluated. The purpose of this study was to evaluate the effect of anthelmintic administration on the fecal microbiome of dogs with and without subclinical Giardia species and Cryptosporidium canis infections.Methodology/Principal findingsPart 1: 6 healthy adult research beagles with subclinical giardiasis and cryptosporidiosis were administered a commercially available preparation of febantel combined with pyrantel and praziquantel (FPP) orally daily for three days. Part 2: 19 healthy staff-owned dogs without giardiasis or cryptosporidiosis were divided into a treatment group (n = 9) that was administered fenbendazole orally daily for five days and an untreated control group (n = 10). For both parts of the study, feces were collected at multiple time points before and after anthelmintic (FPP or fenbendazole) administration. Fecal DNA was extracted for Illumina sequencing of the bacterial 16S rRNA gene and qPCR assays. Neither FPP nor fenbendazole treatment caused a significant change in alpha or beta diversity or the relative abundance of bacterial species. Upon univariate statistical analysis neither FPP or fenbendazole caused minimal changes in the fecal microbiota.ConclusionFPP administration was associated with minimal alterations of the fecal microbiome of healthy research beagles with subclinical giardiasis and cryptosporidiosis. Fenbendazole administration was associated with minimal alterations of the fecal microbiome of healthy staff owned dogs.

Nasal capillariosis due to Eucoleus boehmi in two naturally infected dogs

Summary Herein, we examined two dogs from central Italy with chronic severe upper respiratory signs associated with Eucoleus boehmi eggs shedding at coproscopy. In the first one, improvement in clinical signs was observed after fenbendazole administration, but complete negativity at coprological analysis was gained only after treatment with milbemycin oxyme by mouth. The second one failed to respond to two monthly administrations of a spot-on formulation with imidacloprid/moxidectin, and improvement in clinical signs and negativity at coproscopy were gained only after administration of milbemycin oxyme by mouth. Results here obtained underline the importance to perform further studies to evaluate epidemiological and clinical behavior of this neglected nematode.

Presumptive Albendazole Toxicosis in 12 Alpacas

Presumptive Albendazole Toxicosis in 12 Alpacas

HEMATOLOGIC AND PLASMA BIOCHEMICAL CHANGES ASSOCIATED WITH FENBENDAZOLE ADMINISTRATION IN HERMANN'S TORTOISES (TESTUDO HERMANNI)

Toxicosis associated with benzimidazole anthelmintics has been reported with increasing frequency in zoologic collections. Clinical signs, clinicopathologic abnormalities, and gross and histologic lesions are primarily the result of damage to the gastrointestinal and hematopoietic systems. Profound leukopenia, especially granulocytopenia, is the most common and severe clinicopathologic change associated with benzimidazole administration. Death usually occurs from overwhelming systemic bacterial and/or fungal infections secondary to severe immunosuppression. In this 125-day study, six male Hermann's tortoises (Testudo hermanni) were treated orally with two 5-day courses of fenbendazole 2 wk apart at a dosage of 50 mg/kg. Serial blood samples were used to assess hematologic and plasma biochemical changes before, during, and following the treatment period. Although the tortoises remained healthy, blood sampling indicated an extended heteropenia with transient hypoglycemia, hyperuricemia, hyperphosphatemia, and equivocal hyperproteinemia/hyperglobulinemia, which were considered to be in response to fenbendazole administration. Changes in several other clinicopathologic parameters appeared to correlate with fenbendazole administration. The hematologic and biochemical changes seen in the healthy animals in this study should be considered when treating compromised tortoises with fenbendazole. Hematologic and plasma biochemical status of tortoises/reptiles should be determined before treatment and monitored during the treatment period. The risk of mortality of an individual from nematode infection should be assessed relative to the potential for metabolic alteration and secondary septicemia following damage to hematopoietic and gastrointestinal systems by fenbendazole.

Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys

Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10 mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO 2) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations ( C max) of FBZSO (0.49 μg/mL) and FBZSO 2 (0.60 μg/mL) were detected at ( t max) 5.67 and 8.00 h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33 μg h/mL) was significantly higher than that of the parent drug FBZSO (5.17 μg h/mL). C max of albendazole sulphoxide (ABZSO) (0.08 g/mL) and albendazole sulphone (ABZSO 2) (0.04 μg/mL) were obtained at 5.71 and 8.00 h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84 μg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50 μg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30 h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is concluded that the plasma concentration of FBZSO was significantly higher than that of FBZ and ABZ. Although ABZ is not licensed for use in Equidae, its metabolites presented a greater plasma kinetic profile than FBZ which is licensed for use in horses. A higher metabolic capacity, first-pass effects and lower absorption of benzimidazoles in donkeys decrease bioavailability and efficacy compared to ruminants.

Voltammetric Behavior and Determination by Flow Injection with Amperometric Detection of Benzimidazoles

ABSTRACT The voltammetric behavior of fenbendazole, albendazole, thiabendazole, and mebendazole at a glassy carbon electrode in different aqueous (Britton–Robinson buffer, KOH solutions) and predominantly nonaqueous (acetonitrile:water and methanol:water mixtures) working media is reported. 0.1 M KOH and 70:30 acetonitrile or methanol:water mixtures were selected as most appropriate, the sensitivity achieved for the square wave voltammetric determination of fenbendazole in 0.1 M KOH being much higher than in the predominantly nonaqueous media. Flow‐injection with amperometric detection of the benzimidazoles was evaluated in the three working media. The electrode responded rapidly and the response was constant over sets of 30 measurements at the selected potentials in all cases, RSD values ranging between 1.6% and 4.4%. No significant electrode surface fouling was observed under the hydrodynamic conditions. Detection limits in the 1.0 × 10−8–1.0 × 10−7 M concentration range were achieved. As an application, fenbendazole was determined by flow injection with amperometric detection in spiked feed samples at the 30 and 180 µg g−1 concentration levels, which correspond to the lower and upper concentration for fenbendazole administration to treated poultry. Recoveries of 97 ± 5% and 94 ± 8% were obtained.

Bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in five painted storks

Five painted storks were treated with fenbendazole for 5 days for internal parasitism. Four birds died following treatment. Profound heteropenia was a consistent finding in all samples evaluated; additionally, the 1 surviving bird had progressive anemia. Consistent necropsy findings in the 4 birds that died were small intestinal crypt cell necrosis and severe bone marrow depletion and necrosis. Fenbendazole has been associated with bone marrow hypoplasia and enteric damage in mammals and other species of birds. The dosages of fenbendazole used in birds are often substantially higher than those recommended for mammals, which may contribute to bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in birds.

Pasture deworming and (or) subsequent feedlot deworming with fenbendazole. II, Effects on abomasal worm counts and abomasal pathology of yearling steers

734 steers, weighing 286 kg, were used during a 118-day grazing period, after which 640 were placed in a feedlot for finishing (average of 121 days, range of 111 to 133 days) to measure the main effects and interactions of 2 pasture deworming treatments (negative control, strategically dewormed with fenbendazole) and 2 feedlot deworming treatments (negative control, dewormed with fenbendazole) on faecal egg counts, abomasal worm counts and abomasal pathology. Seven to 10 abomasa from steers on each of the 4 pasture-feedlot treatments (pasture control-feedlot control; pasture control-dewormed in the feedlot; strategically dewormed on pasture-feedlot control; strategically dewormed on pasture-dewormed in the feedlot) were selected at slaughter to determine total worm counts, and to evaluate gross pathology and histopathology of the abomasal mucosa. Pasture deworming with fenbendazole (FBZ) in a strategic programme on days 0, 28 and 56 reduced adult and L4 and EL4 larval stages of Ostertagia ostertagi and adult and L4 stages of Trichostrongylus axei residing in the abomasum at slaughter. Feedlot deworming with FBZ reduced L4 and EL4 stages of O. ostertagi and adult and L4 stages of T. axei. An interaction between pasture deworming treatment and feedlot deworming treatment showed that pasture deworming had a significant effect on reducing the number of Trichostrongylus adult parasites, which was not further reduced by feedlot deworming. Strategic pasture deworming with FBZ followed by FBZ administration at the beginning of the finishing period reduced total O. ostertagi, T. axei and Haemonchus adult and larval stages by 99.13%, compared with untreated controls. There was no relationship between faecal egg counts and total worm counts. Gross pathology showed that strategic deworming on pasture reduced the mean abomasal lesion score at slaughter. An interaction between pasture treatment and feedlot treatment showed that feedlot deworming of pasture control steers reduced mean histopathology score, while feedlot deworming of steers strategically dewormed on pasture had no impact. Distribution of histopathology scores showed that strategic deworming on pasture resulted in more steers without histopathological changes to the abomasal mucosa and fewer steers with higher histopathology scores.

The effectiveness of benzimidazole derivatives for the treatment and prevention of histomonosis (blackhead) in turkeys

The benzimidazole derivatives, albendazole and fenbendazole were evaluated for their effectiveness in the treatment and prevention of histomonosis (blackhead) in turkeys. Histomonosis was produced in 5 week-old birds by placing them on broiler breeder litter known to be contaminated with Heterakis gallinae ova and the protozoan Histomonas meleagridis. In the first trial, at the onset of confirmed clinical disease, birds were treated orally with metronidazole, a compound known to be effective against Histomonas. Those receiving metronidazole had significantly greater mean body weight gains during the treatment period and the 2 weeks following treatment than untreated controls. Treated birds also had significantly lower caecal and liver lesion scores. These findings served to validate the method of disease reproduction and establish its suitability for testing the benzimidazoles. Similar trials were conducted to determine the therapeutic value of albendazole at 100.0 mg/kg of body weight and fenbendazole at 10.0 mg/kg body weight, administered orally twice a day for 5 consecutive days. Under these conditions, both drugs were found to be ineffective as treatments. A final trial was conducted to assess the prophylactic value of albendazole and fenbendazole administration. At the time of placement on contaminated litter, birds were medicated as previously described with the exception that treatment was continued for 14 consecutive days, the approximate incubation period for histomonosis. The trial was terminated on the 16th day. In the case of both albendazole and fenbendazole, treatment was associated with a significant increase in mean body weight gain and lower caecal and liver lesion scores. It is believed that the observed prophylactic effect may be attributed to the destruction of the transport vector e.g., Heterakis larvae, or to direct killing of the flagellated form of Histomonas which is normally found in the caecal lumen and is considered to be more sensitive to chemotherapeutic agents than the amoeboid form found in tissues.

In vivo inhibition of the regenerative capacity of hydatid material after treatment with netobimin.

The effect of netobimin and netobimin plus fenbendazole administration on secondary hydatid disease was studied. Secondary hydatid disease in gerbils (Meriones unguiculatus) was produced by intraperitoneal inoculation of protoscolices of Echinococcus granulosus. The experimental animals received doses of 20 and 50 mg/kg of netobimin or a mixture of netobimin and 1.7 mg/kg of fenbendazole. The results showed that after a single dose of netobimin at the studied concentrations, the cystic material transplanted into the mouse produced a significant recurrence of the disease, but the most remarkable finding was that the hydatid-cyst recurrence never took place when netobimin was given together with fenbendazole.

Survey for drug-resistant gastrointestinal nematodes in 13 commercial sheep flocks

Summary The prevalence of drug-resistant ovine parasites in the United States has not been widely reported. Thirteen flocks, typical of commercial sheep production units, were selected for survey. Four anthelmintics (fenbendazole, ivermectin, pyrantel pamoate, and levamisole) were tested for their ability to reduce herd mean pretreatment fecal egg count. If a properly dosed and administered drug failed to reduce herd mean pretreatment fecal egg count by 80%, it was considered ineffective in that flock, and the presence of parasites resistant to that drug was inferred. Fenbendazole administration changed pretreatment fecal egg counts by +9% to −100%. On the basis of the aforementioned definition, drug resistance existed in 6 of 13 flocks. Posttreatment larval culture indicated that Haemonchus contortus survived administration of fenbendazole. Levamisole, pyrantel pamoate, and ivermectin reduced pretreatment fecal egg count by −83% to −100%; resistance to these products was not evident in the flocks surveyed.

The effect of iron and protein deficiency on plasma levels and parasite uptake of [14C] fenbendazole in rats infected with Nippostrongylus brasiliensis.

The Nippostrongylus brasiliensis-rat model was used to determine whether iron and protein deficiency, which are commonly associated with parasitic infections, affected the pharmacokinetic behaviour of fenbendazole as measured by plasma concentrations and uptake by worms. Plasma 14C concentrations after [14C] fenbendazole administration were higher in iron and protein-deficient rats than in sufficient rats. However, the uptake of 14C by N. brasiliensis in iron and protein-deficient rats was significantly less than in worms from diet-sufficient rats. The reduced anthelmintic uptake by worms in protein and iron-deficient hosts may account, in part, for reduced anthelmintic efficacy under these circumstances. These findings are relevant to understanding variations in response to chemotherapy in populations of parasitised hosts containing malnourished individuals.