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1.
AAPS PharmSciTech ; 25(7): 199, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39198340

RESUMO

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.


Assuntos
Estabilidade de Medicamentos , Fenbendazol , Liofilização , Nanopartículas , Solubilidade , Nanopartículas/química , Fenbendazol/química , Liofilização/métodos , Varredura Diferencial de Calorimetria/métodos , Armazenamento de Medicamentos , Tamanho da Partícula , Difração de Raios X/métodos , Liberação Controlada de Fármacos , Química Farmacêutica/métodos , Poloxâmero/química , Crioprotetores/química
2.
Int J Antimicrob Agents ; 63(5): 107157, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38548248

RESUMO

Cryptococcus neoformans is responsible for over 100 000 deaths annually, and the treatment of this fungal disease is expensive and not consistently effective. Unveiling new therapeutic avenues is crucial. Previous studies have suggested that the anthelmintic drug fenbendazole is an affordable and nontoxic candidate to combat cryptococcosis. However, its mechanism of anticryptococcal activity has been only superficially investigated. In this study, we examined the global cellular response of C. neoformans to fenbendazole using a proteomic approach (data are available via ProteomeXchange with identifier PXD047041). Fenbendazole treatment mostly impacted the abundance of proteins related to metabolic pathways, RNA processing, and intracellular traffic. Protein kinases, in particular, were significantly affected by fenbendazole treatment. Experimental validation of the proteomics data using a collection of C. neoformans mutants led to the identification of critical roles of five protein kinases in fenbendazole's antifungal activity. In fact, mutants lacking the expression of genes encoding Chk1, Tco2, Tco3, Bub1, and Sch9 kinases demonstrated greater resistance to fenbendazole compared to wild-type cells. In combination with the standard antifungal drug amphotericin B, fenbendazole reduced the cryptococcal burden in mice. These findings not only contribute to the elucidation of fenbendazole's mode of action but also support its use in combination therapy with amphotericin B. In conclusion, our data suggest that fenbendazole holds promise for further development as an anticryptococcal agent.


Assuntos
Antifúngicos , Criptococose , Cryptococcus neoformans , Fenbendazol , Proteínas Quinases , Proteômica , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/genética , Antifúngicos/farmacologia , Animais , Fenbendazol/farmacologia , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Camundongos , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Anfotericina B/farmacologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Testes de Sensibilidade Microbiana , Modelos Animais de Doenças , Farmacorresistência Fúngica/genética
3.
Res Vet Sci ; 167: 105113, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141570

RESUMO

The anthelmintic fenbendazole (FBZ) undergoes hepatic S­oxygenation by monooxygenases belonging to the cytochrome P450 (CYP) and flavin-monooxygenase (FMO) families. The in-feed medication with FBZ induced CYP1A-dependent metabolism in pig liver. This fact may alter the metabolism of the anthelmintic itself, and of CYP1A substrates like aflatoxin B1 (AFB1). This work evaluated the effect of the in-feed administration of FBZ on CYP1A-dependent metabolism, on its own pattern of hepatic S­oxygenation, and on the metabolism of AFB1. Landrace piglets remained untreated (n = 5) or received a pre-mix of FBZ (n = 6) in feed for 9 days. Pigs were slaughtered for preparation of liver microsomes used for: CYP content determination; monitoring the CYP1A-dependent enzyme activities, 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD); measurement of FBZ (50 µM) S­oxygenation, and AFB1 (16 nM) disappearance from the incubation medium. In microsomes of FBZ-treated animals, EROD and MROD increased 19-fold (p = 0.002) and 14-fold (p = 0.003), respectively. An enhanced (3-fold, p = 0.004) participation of the CYP pathway in FBZ S­oxygenation was observed in the liver of piglets treated with the anthelmintic (210 ± 69 pmol/min.nmol CYP) compared to untreated animals (68 ± 34 pmol/min.nmol CYP). AFB1 metabolism was 93% higher (p = 0.009) in the liver of FBZ-treated compared to untreated pigs. Positive and significant (p < 0.05) correlations were observed between CYP1A-dependent enzyme activities and FBZ or AFB1 metabolism. The sustained administration of FBZ caused an auto-induction of the CYP1A-dependent S­oxygenation of this anthelmintic. The CYP1A induction triggered by the anthelmintic could amplify the production of AFB1 metabolites in pig liver, including the hepatotoxic AFB1-derived epoxide.+.


Assuntos
Anti-Helmínticos , Citocromo P-450 CYP1A1 , Humanos , Animais , Suínos , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/farmacologia , Fenbendazol/farmacologia , Fenbendazol/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Anti-Helmínticos/farmacologia , Microssomos Hepáticos/metabolismo , Interações Medicamentosas
4.
Vet Res Commun ; 47(2): 803-815, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36542192

RESUMO

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.


Assuntos
Anti-Helmínticos , Fenbendazol , Animais , Feminino , Suínos , Fenbendazol/farmacologia , Fenbendazol/metabolismo , Xenobióticos/metabolismo , Anti-Helmínticos/farmacologia , Anti-Helmínticos/metabolismo , Fígado/metabolismo
5.
Vet Parasitol Reg Stud Reports ; 36: 100810, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36436897

RESUMO

The intensive use of anthelmintics has resulted in resistant parasite populations in horses. The objective of this trial was to evaluate the anthelmintic efficacies of the anthelmintics fenbendazole, ivermectin and abamectin in 24 horse farms in Northern Minas Gerais. Egg counts per gram of faeces (EPG) were performed individually in 619 animals. Animals presenting EPG counts greater than or equal to 150 were used in the tests on faecal egg count reduction (FECR), totalling 436 equines. These animals received the anthelmintics, fenbendazole, ivermectin, and abamectin. Faeces were collected 14 days after the administration of anthelmintics to perform the EPG. Pre- and post-treatment EPG counts were used to calculate the FECR for each anthelmintic group, and faecal culture was used to identificy of the strongyles. The resistance status was evaluated based on the FECR and LCL95%. Fenbendazole was effective in 11 (45.8%) of the horse farms. Ivermectin was effective in 17 (77.3%) and abamectin in 17 (74%) of the farms; side-resistance was detected in 3 (12.5%) of the farms. Intestinal strongyle resistance to anthelmintics was observed in 14 (58.3%) of the farms. Cyathostomin larvae were found in 100% of the farms, Strongylus vulgaris in 13 (54.2%), and S. equinus in 3 (12.5%). Only cyathostomins larvae were detected post-treatment with ivermectin and abamectin.


Assuntos
Anti-Helmínticos , Fenbendazol , Cavalos , Animais , Fenbendazol/uso terapêutico , Ivermectina/uso terapêutico , Contagem de Ovos de Parasitas/veterinária , Brasil , Resistência a Medicamentos , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/farmacologia
6.
Ther Deliv ; 12(8): 597-610, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34286600

RESUMO

Aim: Understanding a drug dissolution process from solid dispersions (SD) to develop formulations with predictable in vivo performance. Materials & methods: Dissolution data of fenbendazole released from the SDs and the control physical mixtures were analyzed using the Lumped mathematical model to estimate the parameters of pharmaceutical relevance. Results: The fit data obtained by Lumped model showed that all SDs have a unique dissolution profile with an error of ±4.1% and an initial release rate 500-times higher than the pure drug, without incidence of drug/polymer ratio or polymer type. Conclusion: The Lumped model helped to understand that the main factor influencing the fenbendazole release was the type formulation (SD or physical mixture), regardless of the type or amount of polymer used.


Assuntos
Fenbendazol , Preparações Farmacêuticas , Liberação Controlada de Fármacos , Polímeros , Solubilidade
7.
AAPS PharmSciTech ; 21(7): 237, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32808055

RESUMO

Valero-fenbendazole (VAL-FBZ) is a novel hybrid compound with in vitro anthelmintic activity, designed and synthesized to address the global problem of resistance to anthelmintic compounds. This new molecule derives from fenbendazole (FBZ), a well-known commercially available benzimidazole used in veterinary medicine despite its poor water solubility. In this work, we report for the first time a strategy to solve the solubility problems of FBZ and VAL-FBZ by means of self-dispersible nanocrystals (SDNC). Nanocrystals were prepared by media milling followed by a spray-drying step, and a comprehensive and exhaustive structural and physicochemical characterization was carried out, in order to understand the systems and their behavior. The formulation poloxamer 188 (P188):FBZ 1:1 turned out with the best process yield (53%) and re-dispersability properties, particle size average of 258 nm, and polydispersity index of 0.2 after redispersion in water. The dissolution profile showed a markedly increased dissolution rate compared with the simple mixture of the components (80% FBZ dissolved in 15 min from the SDNC vs 14% from the control formulation). FTIR spectroscopy, thermal analysis, and X-Ray Powder Diffraction (XRPD) studies showed no chemical interactions between components and an extensive confocal Raman microscopy analysis of the formulations showed very homogeneous spatial distribution of components in the SDNC samples. This manufacturing process was then successfully transferred for preparing and characterizing VAL-FBZ:P188 (1:1) SDNC with similar results, suggesting the promising interest of a novel anthelmintic with improved biopharmaceutical behavior. In conclusion, new FBZ and VAL-FBZ SDNC with improved dissolution rate were successfully prepared and characterized. Graphical abstract.


Assuntos
Fenbendazol/química , Lactamas/química , Nanopartículas/química , Dessecação , Excipientes/química , Tamanho da Partícula , Poloxâmero/química , Difração de Pó , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Água/química
8.
Artigo em Inglês | MEDLINE | ID: mdl-32253211

RESUMO

The human diseases caused by the fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are associated with high indices of mortality and toxic and/or cost-prohibitive therapeutic protocols. The need for affordable antifungals to combat cryptococcal disease is unquestionable. Previous studies suggested benzimidazoles as promising anticryptococcal agents combining low cost and high antifungal efficacy, but their therapeutic potential has not been demonstrated so far. In this study, we investigated the antifungal potential of fenbendazole, the most effective anticryptococcal benzimidazole. Fenbendazole was inhibitory against 17 different isolates of C. neoformans and C. gattii at a low concentration. The mechanism of anticryptococcal activity of fenbendazole involved microtubule disorganization, as previously described for human parasites. In combination with fenbendazole, the concentrations of the standard antifungal amphotericin B required to control cryptococcal growth were lower than those required when this antifungal was used alone. Fenbendazole was not toxic to mammalian cells. During macrophage infection, the anticryptococcal effects of fenbendazole included inhibition of intracellular proliferation rates and reduced phagocytic escape through vomocytosis. Fenbendazole deeply affected the cryptococcal capsule. In a mouse model of cryptococcosis, the efficacy of fenbendazole to control animal mortality was similar to that observed for amphotericin B. These results indicate that fenbendazole is a promising candidate for the future development of an efficient and affordable therapeutic tool to combat cryptococcosis.


Assuntos
Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Animais , Antifúngicos/farmacologia , Criptococose/tratamento farmacológico , Fenbendazol/farmacologia , Virulência
9.
Exp Parasitol ; 204: 107718, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31201779

RESUMO

The aim of the current work was to evaluate a potential pharmacokinetic interaction between the flukicide triclabendazole (TCBZ) and the broad-spectrum benzimidazole (BZD) anthelmintic oxfendazole (OFZ) in sheep. To this end, both an in vitro assay in microsomal fractions and an in vivo trial in lambs parasitized with Haemonchus contortus resistant to OFZ and its reduced derivative fenbendazole (FBZ) were carried out. Sheep microsomal fractions were incubated together with OFZ, FBZ, TCBZ, or a combination of either FBZ and TCBZ or OFZ and TCBZ. OFZ production was significantly diminished upon coincubation of FBZ and TCBZ, whereas neither FBZ nor OFZ affected the S-oxidation of TCBZ towards its sulfoxide and sulfone metabolites. For the in vivo trial, lambs were treated with OFZ (Vermox® oral drench at a single dose of 5 mg/kg PO), TCBZ (Fasinex® oral drench at a single dose of 12 mg/kg PO) or both compounds at a single dose of 5 (Vermox®) and 12 mg/kg (Fasinex®) PO. Blood samples were taken to quantify drug and metabolite concentrations, and pharmacokinetic parameters were calculated by means of non-compartmental analysis. Results showed that the pharmacokinetic parameters of active molecules and metabolites were not significantly altered upon coadministration. The sole exception was the increase in the mean residence time (MRT) of OFZ and FBZ sulfone upon coadministration, with no significant changes in the remaining pharmacokinetic parameters. This research is a further contribution to the study of metabolic drug-drug interactions that may affect anthelmintic efficacies in ruminants.


Assuntos
Anti-Helmínticos/farmacocinética , Benzimidazóis/farmacocinética , Triclabendazol/farmacocinética , Animais , Anti-Helmínticos/metabolismo , Área Sob a Curva , Benzimidazóis/metabolismo , Biotransformação , Sistema Enzimático do Citocromo P-450/metabolismo , Interações Medicamentosas , Fenbendazol/metabolismo , Fígado/metabolismo , Masculino , Microssomos Hepáticos/metabolismo , Oxigenases/metabolismo , Ovinos , Triclabendazol/metabolismo
10.
Braz. J. Pharm. Sci. (Online) ; 55: e17776, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1039048

RESUMO

Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, ß-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-ß-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 µg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-ß-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-ß-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates


Assuntos
Benzimidazóis/administração & dosagem , Ciclodextrinas/farmacocinética , Dissolução/classificação , Solubilidade , Preparações Farmacêuticas , Albendazol/análise , Fenbendazol/análise , Antiparasitários/análise
11.
Vet Parasitol ; 256: 24-28, 2018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29887025

RESUMO

The trematodes of the genus Philophthalmus are eye flukes that cause damage to ocular structures of animals and humans. Despite the increasing number of cases reported in birds, studies related to the diagnosis of subclinical philophthalmosis are lacking, and there are no effective therapeutic regimens available. In the present study, we evaluated the diagnosis and treatment of philophthalmosis in specific pathogen-free chickens (Gallus gallus domesticus) experimentally infected with Philophthalmus gralli. Four chickens were inoculated with metacercariae of P. gralli (20 per eye) obtained from cercariae emerged from naturally infected Melanoides tuberculata. From 90 days post-infection, the chickens were subjected to direct ophthalmic examination (DOE) and conjunctival sac lavage (CSL). The latter technique consisted of lavage of each eye with 200 µL sterile saline solution and subsequent microscopical examination of the collected fluid for the presence of eggs of P. gralli. The anthelminthic treatment protocols included praziquantel (PZQ) at 10, 50, or 100 mg/kg (single dose given intramuscularly), or fenbendazole (FBZ) at 50 mg/kg (three doses at 24 h-intervals given per os). The treatment protocols were performed at 14 day-intervals between each dosage of PZQ. Chickens developed a minimum of one to more than five adult P. gralli per eye, except for one chicken that had a single eye with one parasite. No ocular clinical signs or changes in behavior were noted in any chickens. DOE and CSL were considered techniques with similar sensitivity for the diagnosis of avian philophthalmosis. The data suggested that PZQ and FBZ, at the dosages and schedules employed, are not effective for the complete elimination of P. gralli. CSL is proposed as a complementary technique for the diagnosis and monitoring of philophthalmosis post-treatment, especially in subclinical cases. The evaluation of new protocols, routes of administration, and anthelmintic drugs are needed for successful pharmacological treatment of philophthalmosis.


Assuntos
Fenbendazol/uso terapêutico , Doenças das Aves Domésticas/diagnóstico , Doenças das Aves Domésticas/tratamento farmacológico , Praziquantel/uso terapêutico , Infecções por Trematódeos/veterinária , Animais , Anti-Helmínticos/uso terapêutico , Galinhas , Olho/parasitologia , Resultado do Tratamento , Trematódeos/fisiologia , Infecções por Trematódeos/diagnóstico , Infecções por Trematódeos/tratamento farmacológico
12.
J Vet Pharmacol Ther ; 41(3): 476-484, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29465161

RESUMO

Parasitic diseases have a significant impact on livestock production. Nematodicidal drugs, such as fenbendazole (FBZ) or its oxidized metabolite oxfendazole (OFZ), can be used along with the trematodicidal triclabendazole (TCBZ), to broaden the spectrum of anthelmintic activity. However, co-exposure to these compounds could lead to drug-drug (D-D) interactions and eventually alter the clinical profile of each active principle. The aim of this study was to assess the presence of such interactions by means of two in vitro models, namely bovine liver microsomal fractions and bovine precision-cut liver slices (PCLSs). To this end, an in vitro assessment involving incubation of FBZ and TCBZ or a combination of FBZ and TCBZ was carried out. Results with microsomal fractions showed a 78.4% reduction (p = .002) in the rate of OFZ production upon co-incubation, whereas the sulfoxide metabolite of TCBZ (TCBZSO) exhibited a decreasing tendency. With PCLS, OFZ accumulation in the incubation medium increased 1.8-fold upon co-incubation, whereas TCBZSO accumulation decreased by 28%. The accumulation of FBZ and OFZ in the liver tissue increased upon 2-hr co-incubation, from 2.1 ± 1.5 to 18.2 ± 6.1 (p = .0009) and from 0.4 ± 0.1 to 1.3 ± 0.3 nmol (p = .0005), respectively. These results confirm the presence of D-D interactions between FBZ and TCBZ. Further studies are needed to determine the extent of involvement of drug-metabolizing enzymes and membrane transporters in interactions between compounds largely used in livestock production systems.


Assuntos
Benzimidazóis/farmacocinética , Bovinos , Fenbendazol/farmacocinética , Fígado/metabolismo , Microssomos Hepáticos/metabolismo , Albendazol/farmacocinética , Animais , Anti-Helmínticos/farmacocinética , Interações Medicamentosas , Manejo de Espécimes , Triclabendazol
13.
Vet Parasitol Reg Stud Reports ; 13: 220-223, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-31014878

RESUMO

Anthelmintic resistance in equine cyathostomins has been described worldwide, with resistance to the benzimidazole class being particularly widespread. The status of anthelmintic efficacy in Cuba has been virtually unknown due to the lack of equine labelled products. One recent report documented suboptimal efficacy levels of extra-label albendazole products against cyathostomins, but it remains unknown to which extent benzimidazole resistance exists in the population. The aim of the present study was to evaluate the anthelmintic efficacy of two benzimidazole products labelled for equines, fenbendazole and oxibendazole. A fecal egg count reduction test (FECRT) was carried out on 132 horses aged 4 months to 18 years in 14 herds, belonging to six provinces. Ten herds exhibited signs of resistance to at least one of the benzimidazoles (mean FECRT<90%). Overall, oxibendazole exhibited higher efficacy than fenbendazole (p = 0.0062), and higher efficacy levels were found in horses never dewormed before compared to those treated within 3-12 months prior to the study (p = 0.0015). Pre-treatment larval cultures revealed the presence of large strongyles and cyathostomin larvae in all herds, while only cyathostomin larvae were detected post treatment. The present work is the first report of anthelmintic resistance in equine cyathostomins in Cuba, and suggests pre-selection for resistant strains by extra-label use of albendazole on the studied farms.


Assuntos
Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Resistência a Medicamentos , Infecções Equinas por Strongyloidea/tratamento farmacológico , Strongyloidea/efeitos dos fármacos , Animais , Benzimidazóis/farmacologia , Cuba , Fezes/parasitologia , Feminino , Cavalos/parasitologia , Masculino , Contagem de Ovos de Parasitas/veterinária
14.
Parasitol Res ; 116(3): 939-944, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28039497

RESUMO

In this study were proposed different protocols for the treatment of mice naturally infected with Giardia muris. Male Swiss mice were divided into seven groups, with five animals each, in a blind, controlled, randomized by drawing lots and once-repeated experiment. Parasite detection and cure control were performed using the Faust method and search by trophozoites in the intestinal mucosa. Clinical parameters (weight, water and feed consumption, elimination of excreta, aspect of the fur and feces) were also evaluated. All animals were treated with metronidazole (M), fenbendazole (F), and probiotics (P), administered intragastrically, during 7 days. M1, FM1, and F1 groups were treated 1×/day; M3, FM3, and PM3 groups 3×/day; and ST (control group) received only water. After the 5th and 7th days of treatment, the animals in FM1/FM3 and PM3/M3 groups presented, respectively, negative results and remained negative in the following 10 days. Animals in F1 group consumed less water (p = 0.00010) compared with FM1/FM3/PM3. The animals in M1 group compared with FM3/M3, F1 compared with M3, and ST compared with FM1/FM3/M3/PM3 consumed a larger amount of feed (p = 0.00001). The animals in F1 group compared with FM3/M1/M3/PM3, FM1 compared with FM3, and ST compared with FM3/M1/M3/PM3 eliminated lower volume of excreta (p = 0.00001). The results show that the association between F and M potentiates the effects, indicating a synergistic action of these two drugs, and FM1 is the best protocol due to early negativity in the animals, lower concentrations of the drugs, lower risk of toxicity and stress, and less alterations in clinical parameters.


Assuntos
Antiprotozoários/administração & dosagem , Fenbendazol/administração & dosagem , Giardia/efeitos dos fármacos , Giardíase/tratamento farmacológico , Metronidazol/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Sinergismo Farmacológico , Fezes/parasitologia , Feminino , Giardia/fisiologia , Giardíase/parasitologia , Giardíase/fisiopatologia , Humanos , Mucosa Intestinal/parasitologia , Masculino , Camundongos , Trofozoítos/efeitos dos fármacos , Trofozoítos/fisiologia
15.
Rev. bras. ciênc. vet ; 18(2-3): 2-3, 2011.
Artigo em Português | LILACS-Express | LILACS, VETINDEX | ID: biblio-1491448

RESUMO

The gastrointestinal parasitoses of domestic animals have a great impact on the hematological status but nonethelessresearch on this subject concerning buffaloes is rare. Thus, the blood profile of buffalo calves naturally infected by parasitesfrom the seventh to the 300th day of life. Animals were distributed in three experimental groups treated with ivermectin,fenbendazole, and placebo, respectively. Changes of hematological parameters were related to the presence of adultgastrointestinal nematodes, which were diagnosed and identified by the presence of eggs in the feces of wormed animals ascompared to those medicated.

16.
R. bras. Ci. Vet. ; 18(2-3): 2-3, 2011.
Artigo em Português | VETINDEX | ID: vti-712658

RESUMO

The gastrointestinal parasitoses of domestic animals have a great impact on the hematological status but nonethelessresearch on this subject concerning buffaloes is rare. Thus, the blood profile of buffalo calves naturally infected by parasitesfrom the seventh to the 300th day of life. Animals were distributed in three experimental groups treated with ivermectin,fenbendazole, and placebo, respectively. Changes of hematological parameters were related to the presence of adultgastrointestinal nematodes, which were diagnosed and identified by the presence of eggs in the feces of wormed animals ascompared to those medicated.

17.
Semina Ci. agr. ; 29(1): 175-178, 2008.
Artigo em Português | VETINDEX | ID: vti-472625

RESUMO

This study aimed to evaluate the efficacy of metronidazole, fenbendazole and secnidazole against Giardia muris in mice naturally infected. Forty mice of the species Mus musculus were divided in four groups of ten each, being group A non treated, the control group and groups B, C and D treated with 4mg/ml of metronidazole, fenbendazole and secnidazole, respectively. Two feces collection, on day 0 and on day 10 after treatment, were done in order to evaluate the efficacy of the drugs. Samples were analyzed by the centrifugal-flotation method with zinc sulfate. Efficacy of 97,05% for metronidazole, 98,30% for fenbendazole and 100% for secnidazole were observed in the study. According to the results it was concluded that the tested drugs were effective for the treatment of mice parasitized by Giardia muris.


Este estudo visou avaliar a eficácia do metronidazol, fenbendazole e secnidazol contra Giardia muris em camundongos naturalmente infectados. Foram utilizados 40 camundongos da espécie Mus musculus divididos em quatro grupos de 10 animais cada, sendo grupo A, grupo controle, não tratados, e grupos B, C e D tratados com 4mg/ml de metronidazol, fenbendazole e secnidazol, respectivamente. Para avaliar a eficácia dos medicamentos foram realizadas duas coletas de fezes uma no dia zero e outra 10 dias após tratamento. As amostras foram processadas e analisadas a partir do método de centrífugo-flutuação com sulfato de zinco. No estudo observou-se eficácia de 97,05% para metronidazol, 98,30% para fenbendazole e 100% para secnidazol no tratamento de giardiase murina. Com base nos resultados concluí-se que as drogas testadas apresentaram eficácia no tratamento de camundongos parasitados por Giardia muris.

18.
Braz. j. vet. res. anim. sci ; 20(1): 43-52, 1983.
Artigo em Português | LILACS-Express | VETINDEX | ID: biblio-1470250

RESUMO

The efficacy of Fenbendazole and Mebendazole against strongyle infections was evaluated in a controlled trial using 23 naturally infected mares. Such equines, aged from three to eighteen years, cross-bred and field-raised, were distributed in three groups, each with similar pre-treatment fecal egg counts. Group A: 8 received a single dose of granulated Fenbendazole at the level of 7,5 mg/kg, with the fodder. Group B: 8 received a single dose of granulated Mebendazole at the level of 2,000 mg/ animal, with the fodder and Group C: 7 being left as untreated controls. Worm differential larval counts were made on feces at: -12, - 8, - 4, 0, 1, 2, 3, 11, 18, 25, 31, 45 and 60 days of treatment. Fecal samples were collected at 24, 48 and 72 hours posttreatment. Alfortia edentata, Delafondia vulgaris, Strongylus equinus and small strongyles were recovered from such fecal samples. A significant reduction in the mean output of strongyle eggs posttreatment occurred in the Groups A and B. This reduction was larger and more lasting in Group A than in Group B.


Utilizaram-se éguas mestiças Puro Sangue Inglês (PSD, com variados graus de mestiçagem, com três a 18 anos de idade, criadas a campo e distribuídas em três grupos: A - oito que receberam 7,5 mg/kg de Fenbendazol imetil-5-(fenil-tio)-benzimidazol-2- -carbamato), misturado à ração; B - oito, tratados com Mebendazol (metil-5(6)-benzol-2-benzimidazole carbamato) na dose de 2.000 mg/animal, também na ração e C - sete sem qualquer tratamento (grupo testemunha). As médias dos números de ovos por grama de fezes (OPG), antes dos tratamentos, eram semelhantes nos três grupos. Foram feitas contagens de OPG, coproculturas e identificação de larvas nos dias 12, 8 , 4, 0 ,1 , 2, 3 ,1 1 ,1 8 , 25, 31 e 60 dos tratamentos, bem como colheitas de helmintos de amostras de fezes, retiradas do reto de cada animal às 24, 48 e 72 horas pós-tratamentos. Os helmintos identificados foram Alfortia edentata, Dela fondia vulgaris, Strongylus equinus e pequenos estrôngilos. As médias das contagens de OPG pós-tratamentos indicaram que nos grupos A e B ocorreram reduções significativas nas contagens e que em A foi maior e mais duradoura que em B.

19.
Braz. j. vet. res. anim. sci ; 20(1): 43-52, 1983.
Artigo em Português | VETINDEX | ID: vti-727208

RESUMO

The efficacy of Fenbendazole and Mebendazole against strongyle infections was evaluated in a controlled trial using 23 naturally infected mares. Such equines, aged from three to eighteen years, cross-bred and field-raised, were distributed in three groups, each with similar pre-treatment fecal egg counts. Group A: 8 received a single dose of granulated Fenbendazole at the level of 7,5 mg/kg, with the fodder. Group B: 8 received a single dose of granulated Mebendazole at the level of 2,000 mg/ animal, with the fodder and Group C: 7 being left as untreated controls. Worm differential larval counts were made on feces at: -12, - 8, - 4, 0, 1, 2, 3, 11, 18, 25, 31, 45 and 60 days of treatment. Fecal samples were collected at 24, 48 and 72 hours posttreatment. Alfortia edentata, Delafondia vulgaris, Strongylus equinus and small strongyles were recovered from such fecal samples. A significant reduction in the mean output of strongyle eggs posttreatment occurred in the Groups A and B. This reduction was larger and more lasting in Group A than in Group B.  


Utilizaram-se éguas mestiças Puro Sangue Inglês (PSD, com variados graus de mestiçagem, com três a 18 anos de idade, criadas a campo e distribuídas em três grupos: A - oito que receberam 7,5 mg/kg de Fenbendazol imetil-5-(fenil-tio)-benzimidazol-2- -carbamato), misturado à ração; B - oito, tratados com Mebendazol (metil-5(6)-benzol-2-benzimidazole carbamato) na dose de 2.000 mg/animal, também na ração e C - sete sem qualquer tratamento (grupo testemunha). As médias dos números de ovos por grama de fezes (OPG), antes dos tratamentos, eram semelhantes nos três grupos. Foram feitas contagens de OPG, coproculturas e identificação de larvas nos dias 12, 8 , 4, 0 ,1 , 2, 3 ,1 1 ,1 8 , 25, 31 e 60 dos tratamentos, bem como colheitas de helmintos de amostras de fezes, retiradas do reto de cada animal às 24, 48 e 72 horas pós-tratamentos. Os helmintos identificados foram Alfortia edentata, Dela fondia vulgaris, Strongylus equinus e pequenos estrôngilos. As médias das contagens de OPG pós-tratamentos indicaram que nos grupos A e B ocorreram reduções significativas nas contagens e que em A foi maior e mais duradoura que em B.

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