Fosfatriclaben, a prodrug of triclabendazole: Preparation, stability, and fasciolicidal activity of three new intramuscular formulations.

In this study, we present the preparation, stability, and in vivo fasciolicidal activity of three new intramuscular formulations in sheep of a prodrug based on triclabendazole, named fosfatriclaben. The new formulations were ready-to-use aqueous solutions with volumes recommended for intramuscular administration in sheep. The use of poloxamers (P-407 and P-188) and polysorbates (PS-20 and PS-80) in the new formulations improved the aqueous solubility of fosfatriclaben by 8-fold at pH 7.4. High-performance liquid chromatography with UV detection was used to evaluate the stability of fosfatriclaben in the three formulations. High recovery (> 90%) of fosfatriclaben was found for all formulations after exposure at 57 ± 2 °C for 50 h. The three intramuscular formulations showed high fasciolicidal activity at a dose of 6 mg/kg, which was equivalent to the triclabendazole content. The fasciolicidal activity of fosfatriclaben was similar to commercial oral (Fasimec®) and intramuscular (Endovet®) triclabendazole formulations at a dose of 12 mg/kg. In the in vivo experiments, all formulations administered intramuscularly reduced egg excretion by 100%, and formulations F1, F2, and F3 presented fasciolicidal activities of 100%, 100%, and 99.6%, respectively.

Evaluation of the ovicidal activity and fasciolicidal activity of the extract of ethyl acetate from Artemisia ludoviciana Nutt. spp. mexicana and of artemisinin against adult parasites of Fasciola hepatica.

The objective of this work was to evaluate the effect of the ethyl acetate extract from A. ludoviciana (EALM) and artemisinin against adult parasites and eggs of F. hepatica. For the ovicidal assay, cell culture plates with 24 wells were used, and 90 to 110 F. hepatica eggs were placed in each well. The eggs were exposed to concentrations of 100, 200, 300, 400, and 500 mg/L EALM and incubated for 16 days. Additionally, triclabendazole (TCBZ) was used as a reference drug at concentrations of 10 and 50 mg, and the response of artemisinin at concentrations of 10 and 20 mg was simultaneously assessed. Adult flukes were exposed to concentrations of 125, 250, 375, and 500 mg/L EALM. The results of the ovicidal action of EALM on the eggs showed that concentrations greater than 300 mg/L were significant, with ovicidal percentages greater than 60% observed on day 16 of incubation (p < 0.05). The maximum efficiency of EALM on adult flukes was reached 72 h post-exposure at a concentration of 125 mg/L (p < 0.05).

Field study on the determination of the effective dose of injectable fosfatriclaben prodrug in sheep naturally infected with Fasciola hepatica.

The aim of the present study was to determine the effective dose of fosfatriclaben through a field study in sheep naturally infected with F. hepatica. Thirty crossbred sheep positive for fluke eggs were selected for inclusion in the trial. On day 0, 5 groups of 6 animals each were formed for treatments: group 1 (G1), G2, and G3 received fosfatriclaben at 4, 6, and 8 mg/kg/IM, respectively. G4 received triclabendazole at 10 mg/kg/PO, and G5 was the untreated control group. Fecal samples of the sheep were analyzed to count the number of fluke eggs to evaluate the percentage of egg reduction. Twenty-one days after treatment, all sheep were humanely euthanized to extract the flukes from the bile ducts. They were counted to assess the percentage of fluke reduction. Fosfatriclaben reduced fluke eggs by 99.6, 99.6, and 100% and flukes by 94.3, 100, and 100%, respectively. Triclabendazole reduced fluke eggs by 95.2% and flukes by 100%. The fosfatriclaben injectable prodrug showed a high fasciolicidal efficacy similar to triclabendazole, with advantages over its predecessor, since only half the dose as compared to triclabendazole was required to remove eggs and flukes in the sheep that were studied.

Effectiveness of an experimental injectable prodrug formulation against Fasciola hepatica of different ages in experimentally infected sheep.

In this work, we present an evaluation of the fasciolicidal efficacy of a new injectable formulation of fosfatriclaben in comparison with the subcutaneous closantel and oral triclabendazole formulations currently used in veterinary practice as fasciolicides. The study was carried out in vivo on Fasciola hepatica at 2, 4, 6 and 8 weeks of age in experimentally infected sheep. To evaluate the formulation, the percent reduction of the parasite load was measured and the number of fluke eggs. Fosfatriclaben was used at 6 mg/kg/IM (dose equivalent to triclabendazole content), closantel at 5% at 10 mg/kg/SC, and triclabendazole at 10 mg/kg/PO; the control group received no treatment. Fosfatriclaben showed fasciolicidal efficacies of 95.5 %, 100 %, 100 % and 100 %, and triclabendazole showed similar efficacies of 97.4 %, 100 %, 100 % and 100 %, at the different treatment weeks (P > 0.05). Closantel showed limited efficacy against 2-, 4- and 6-week-old flukes but 100 % efficacy in adult flukes. All three evaluated formulations eliminated all 8-week-old F. hepatica trematode eggs. Although fosfatriclaben and triclabendazole showed similar fasciolicidal efficacy, the intramuscular administration of fosfatriclaben has several advantages over the oral administration of triclabendazole, such as ease of administration for veterinary use and a reduced risk of accidents for both the operator and the animals. In addition, the dose used in this injectable formulation is only 60 % of the oral dose, which reduces environmental contamination.

Efficacy of purified fractions of Artemisia ludoviciana Nutt. mexicana and ultraestructural damage to newly excysted juveniles of Fasciola hepatica in vitro.

The study aimed to evaluate the fasciolicidal efficacy of extracts and fractions of Artemisia ludoviciana and identify the active substance. Extracts from A. ludoviciana were obtained by using hexane, ethyl acetate and methanol. To test the extracts, newly excysted juveniles of Fasciola hepatica were artificially obtained. The extracts were tested at concentrations of 125, 250, 375 and 500 mg/L. In each test run, an untreated control group and control wells containing triclabendazole sulfoxide were also included. The flukes were examined at 24, 48 and 72 h after treatment. Ethyl acetate extract (ALEAE) showed 100 % efficacy at 48 h of exposure (P < 0.05). Then, this extract was fractionated by column chromatography (CC), and the obtained fractions were evaluated in vitro as previously mentioned. The results indicated that fraction 3 yielded 100 % efficacy at 48 h (P < 0.05). Subsequently, the purification of fraction 3 was performed. New fractions were obtained (A-L), with sub-fraction "J" exhibiting 100 % efficacy at 24 h (P < 0.05). These sub-fractions were submitted to phytochemical analysis, demonstrated the presence of sesquiterpene lactones. Likewise, were analyzed by HPLC/MS/DAD, and the results showed that artemisinin was the main compound. In addition, flukes treated were examined by scanning electron microscopy (SEM) showing areas of inflammation throughout the tegument.

Efficiency comparison of experimental fosfatriclaben with three commercial fasciolicides in experimentally infected sheep.

In this work, we compare and evaluate the efficiency of fosfatriclaben with three commercial fasciolicides in experimentally infected sheep. Fosfatriclaben is a novel prodrug derived from triclabendazole; it is highly water-soluble with excellent aqueous stability at pH 7, properties that make it ideal for developing intramuscular pharmaceutical compositions in the form of solutions. In order to compare, 30 mixed breed sheep, previously diagnosed negative to fluke eggs, were infected with 200 metacercariae of Fasciola hepatica, twice. Five groups of six animals/each were formed for treatments. Group 1 (G1) was treated with closantel 5% injectable at 5 mg/kg subcutaneously, G2 with clorsulon at 2 mg/kg subcutaneously, G3 with triclabendazole at 12 mg/kg per os, G4 with fosfatriclaben at 6 mg/kg intramuscularly (dose equivalent to triclabendazole content), and G5 remained as the non-treated control. On day 110, fecal samples were examined to determine the percentage of egg reduction after treatment, and sheep were humanely euthanized. The livers were collected, the flukes were extracted, measured, and counted. Efficiency in egg reduction was of 86.8, 90.5, 98.4, and 97.3% for closantel, clorsulon, triclabendazole, and fosfatriclaben, respectively, and efficiency against flukes was of 96.2, 91.9, 99.4, and 95.7%, respectively. No statistical differences were found between treatments. It is concluded that fosfatriclaben at 6 mg/kg intramuscularly presented a high fasciolicide efficiency, similar to the best commercial fasciolicides, having advantage over its predecessor since it uses half of the dose required by triclabendazole to remove flukes in sheep under study.

First database of the spatial distribution of Eimeria species of cattle, sheep and goats in Mexico.

Ruminant coccidiosis is a gastrointestinal disease caused by parasites of the genus Eimeria. Environmental and climatic factors are relevant for the development, survival, and transmission of coccidiosis because Eimeria oocysts are able to survive in the environment for several weeks or months in favorable conditions of moderate heat and moisture. The aim of the present study was to georeference, for the first time, the locations of Eimeria occurrences in Mexico from 1961 to 2018. A dataset was created for 3414 reports of Eimeria occurrences in cattle, sheep, and goats in Mexico. Twelve species of Eimeria that infect cattle were recorded, 11 Eimeria species of sheep are present in Mexico, and eight species of goats are geographically distributed in the country. In the current findings, it has been observed that Eimeria colonizes mainly the temperate semihumid, temperate humid, warm humid, and warm semihumid areas during spring and summer in animals younger than 1 year of age. Macroenvironmental variables like temperature and rainfall influence the prevalence of Eimeria in cattle, sheep, and goats, and for some species, the rearing system, facility type, farm size, and altitude affect the occurrence of this parasite. Results may support future studies aimed at reducing the disease prevalence of the parasite in endemic regions of Mexico. The use of recorded cases and climate variables yields a more comprehensive perspective of the epidemiology of eimeriosis, which would be difficult to infer from laboratory studies alone.

Development of the first georeferenced map of Rhipicephalus (Boophilus) spp. in Mexico from 1970 to date and prediction of its spatial distribution.

The tick genus Ripicephalus (Boophilus), particularly R. microplus, is one of the most important ectoparasites that affects livestock health and considered an epidemiological risk because it causes significant economic losses due, mainly, to restrictions in the export of infested animals to several countries. Its spatial distribution has been tied to environmental factors, mainly warm temperatures and high relative humidity. In this work, we integrated a dataset consisting of 5843 records of Rhipicephalus spp., in Mexico covering close to 50 years to know which environmental variables mostly influence this ticks' distribution. Occurrences were georeferenced using the software DIVA-GIS and the potential current distribution was modelled using the maximum entropy method (Maxent). The algorithm generated a map of high predictive capability (Area under the curve = 0.942), providing the various contribution and permutation importance of the tested variables. Precipitation seasonality, particularly in March, and isothermality were found to be the most significant climate variables in determining the probability of spatial distribution of Rhipicephalus spp. in Mexico (15.7%, 36.0% and 11.1%, respectively). Our findings demonstrate that Rhipicephalus has colonized Mexico widely, including areas characterized by different types of climate. We conclude that the Maxent distribution model using Rhipicephalus records and a set of environmental variables can predict the extent of the tick range in this country, information that should support the development of integrated control strategies.

Novel triclabendazole prodrug: A highly water soluble alternative for the treatment of fasciolosis.

In this work we present the synthesis, aqueous solubility and stability, hydrolysis by alkaline phosphatase, and in vivo fasciolicidal activity in sheep of a highly water soluble phosphate salt prodrug of triclabendazole (MFR-5). The aqueous solubility of MFR-5 at pH 7 was 88,000-fold that of triclabendazole. MFR-5 showed excellent aqueous stability (>95% after 26h) at pH 7, making it ideal for developing pharmaceutical compositions in the form of solutions that can easily be hydrolyzed by the enzyme alkaline phosphatase (t=13.6s) to liberate the precursor compound. An aqueous solution of MFR-5 administered intramuscularly to sheep at concentrations of 4, 6 and 8mg/kg presented a fasciolicidal efficiency of 96.5%, 98.4% and 99.2%, respectively. In the in vivo experiments, MFR-5 reduced 100% the excretion of eggs in all of the above concentrations.

In vitro antihelmintic effect of fifteen tropical plant extracts on excysted flukes of Fasciola hepatica.

BACKGROUND: Fasciolosis due to Fasciola hepatica is the most important hepatic disease in veterinary medicine. Its relevance is important because of the major economical losses to the cattle industry such as: reduction in milk, meat and wool production; miscarriages, anemia, liver condemnation and occasionally deaths, are estimated in billons of dollars. The emergence of fluke resistance due to over or under dosing of fasciolides as well as environmental damage produced by the chemicals eliminated in field have stimulated the need for alternative methods to control Fasciola hepatica. The aim of this study was to evaluate the in vitro anthelmintic effect of fifteen tropical plant extracts used in tradicional Mexican medicine, on newly excysted flukes of Fasciola hepatica. RESULTS: The flukes were exposed in triplicate at 500, 250 and 125 mg/L to each extract. The efficacy was assessed as the mortality rate based on the number of live and dead flukes after 24, 48 and 72 h post-exposure. The plants with anthelmintic effect were evaluated once again with a concentration of 375 mg/L in order to confirm the results and to calculate lethal concentrations at 50%, 90% and 99% (LC(50), LC(90), and LC(99)). Plant extracts of Lantana camara, Bocconia frutescens, Piper auritum, Artemisia mexicana and Cajanus cajan had an in vitro anthelmintic effect (P <0.05). The LC(50), LC(90) and LC(99) to A. mexicana, C. cajan and B. frutescens were 92.85, 210.44 and 410.04 mg/L, 382.73, 570.09 and 788.9 mg/L and 369.96, 529.94 and 710.34 mg/L, respectively. CONCLUSION: It is concluded that five tropical plant extracts had promising anthelmintic effects against F. hepatica. Further studies on toxicity and in vivo biological evaluation in ruminant models might help to determine the anthelmintic potential of these plant extracts.

A highly water soluble benzimidazole derivative useful for the treatment of fasciolosis.

This study describes the synthesis of compound (7), a highly hydrosoluble phosphonooxymethyl prodrug of compound alpha (4). Compound (7) improved the aqueous solubility of its precursor compound (4) by 50,000 times and it is stable at neutral pH. The prodrug showed faciolicidal activity when evaluated in vitro against excysted Fasciola hepatica metacercariae. The in vivo evaluation of (7) was carried out via oral, intramuscular and subcutaneous administration in sheep artificially infected with F. hepatica metacercariae. At an intramuscular dose of 4 mg/kg, the activity of (7) was similar to that of compound alpha (4) at an oral dose of 15 mg/kg.

Design, synthesis, in vitro evaluation and preliminary SAR studies of N-(2-(heteroaryloxy)propyl)phenothiazines against Rhipicephalus microplus cattle tick.

A family of 15 N-substituted phenothiazines was designed, synthesized and their acaricidal activity against Rhipicephalus microplus was determined in vitro. The synthetic methodology is simple and can be employed in multigram scale. The rationale for the structure-based design of these compounds is the potential for azines and phenothiazine to engage in π-π interactions; these fragments, joined together by a short, flexible alkoxide linker, structurally resemble phenothiazine-based cholinesterase inhibitors, while their weak basicity implies a neutral active form, rather than a cationic one, thus facilitating penetration of the cuticle of ticks. One compound displayed excellent acaricidal activity (LD50=0.58 µg/mL). Preliminary SAR analysis suggests that the activity is influenced by the presence of a weakly basic nitrogen atom, as well as the substitution pattern within the heterocycles.

Solubilidad de un compuesto con actividad fasciolicida: evaluación de eficacia in vitro y en ovinos experimentalmente infectados con Fasciola hepatica / Solubility of a compound with fasciolicidal activity: evaluation of efficacy in vitro and experimentally on infected sheep with Fasciola hepatica

Compound alpha (Ca) is a benzimidazolic derívate which has shown a high fasciolicidal efficacy when it is given by oral via. Solubilization of Ca would be a suitable alternative to obtain an injectable formulation. The objectives of the present study were to evaluate the solubility of Ca in order to determine the in vitro fasciolicidal efficacy and experimentally on infected ovines. The assays of solubility quantified by high-performance liquid chromatography (HPLC), showed that beta-cyclodextrin (β-CD) and hydroxi-propylbeta-cyclodextrin (HP-β-CD) solubilized in 0.015% and 1.018% respectively. The solubilization for HP-β-CD was calculated as 3.95% for 5.8 mg; 10.76% for HP-β-CD with methanol, 39.048% for proylene-glycol (PG), 100% for glycerol formal (GF), and 100% for combined PG and GF and water in proportions of 3:2:5 and 3:2:4. In vitro evaluation using immature F. hepatica showed that Ca induced 100% efficacy 24 hours after solubilization with either GF or GF combined with PG and water. The efficacy in sheep was 56.4 and 68.4% at 1 and 2 mg/kg respectively; whereas 1 mg/kg of sulphoxide metabolite induced an efficacy of 73.9%. The HPLC assays performed showed no evidence of the sulphoxide and sulphone metabolites. It is concluded that besides solubility and high in vitro fasciolicidal efficacy, the in vivo results in sheep showed only a moderate efficacy.

El compuesto alfa es un derivado bencimidazólico de gran eficacia fasciolicida, que se ingiere vía oral, su solubilización constituye una alternativa para obtener una formulación inyectable. Los objetivos de este estudio fueron: evaluar la solubilidad del compuesto alfa, determinar la eficacia fasciolicida in vitro y en ovinos experimentalmente infectados. Los ensayos de solubilidad que fueron cuantificados mediante cromatografía de líquidos de alta resolución, mostraron que la betaciclodextrina e hidroxipropil-betaciclodextrina solubilizaron en 0.051% y 1.018%. Esta última se evaluó con cinco concentraciones, mostró que a 5.8 mg la solubilidad fue 3.95%; hidroxipropil-betaciclodextrina y metanol, 10.76%; propilén-glicol, 39.048%; glicerol formal, 100%; y glicerol formal con propilén-glicol y agua en proporciones 3:2:5 y 3:2:4, 100%. La evaluación in vitro con fasciolas inmaduras mostró que el compuesto con glicerol formal y la combinación de vehículos a las 24 horas fueron eficaces en 100%. La eficacia in vivo en ovinos mostró que el compuesto alfa a dosis de 1 mg/kg fue de 56.46%, a 2 mg/kg de 68.4% y con sulfóxido del compuesto alfa a 1 mg/kg de 73.9%. No se encontró el compuesto alfa ni sus metabolitos sulfóxido y sulfona en el suero determinado por medio del cromatógrafo de líquidos de alta resolución. Se concluye que a pesar de obtener solubilidad del compuesto alfa y alta eficacia fasciolicida in vitro, los resultados in vivo en ovinos revelaron eficacia moderada.

In vitro fasciolicide activity of some plant extracts against newly excysted flukes.

The aim of the present study was to evaluate, under in vitro conditions, the activity of 20 plant extracts against newly excysted Fasciola hepatica metacercariae. The plants were selected on the basis of anthelmintic activity, traditional use, availability, solubility, and permanence in the liver. For the in vitro evaluation, 24-well Nunc-immunoplates containing RPMI-1640 culture medium bovine sera plus antibiotics were used. Extract concentrations of 500 and 50 mg/mL were placed in triplicate. Approximately 10 newly excysted flukes were placed in each well, and the plates were incubated in a CO(2) incubator at 5% atmosphere for 3 days. In each plate four control wells containing nontreated flukes were included. All procedures were undertaken under an air-flow cabinet. Efficacy was measured on days 1 and 3 by considering the motility of the live or dead trematodes evaluated with the aid of an inverted microscope. Results indicated that, from all extracts evaluated, Tilia mexicana showed an average efficacy for concentrations of 500 and 50 mg/mL, respectively, of 100 and 100%; Eriobotrya japonica, 100 and 95%; Coffea arabica, 100 and 100%; Crataegus mexicana, 95 and 90%; and Ternstroemia pringlei 100 and 100%. From this preliminary evaluation, we conclude that further and more detailed evaluations at lower concentrations should be undertaken to understand the real efficacy of these plant extracts.

In silico fasciolicide activity of three experimental compounds in sheep.

The aim of the present study was to evaluate the fasciolicide activity of three experimental drugs, selected by an in silico system called TOMOCOMD-CARDD, in sheep. Drugs were identified by the computer system, and, after statistical selection, 24 Pelibuey sheep were infected on days 0 and 30, each with 200 metacercariae of Fasciola hepatica. When the infection reached 8 and 4 weeks of age, respectively, four groups of six animals each were formed. Group 1 received thiacetazone 150 mg/animal/p.o. Group 2 was treated with 3,5,5, trimethyloxazolidine 2,4-dione at 450 mg/animal/p.o. G3 received guanabenz acetate at a dose of 1.5 mg/animal/p.o. G4 served as an untreated control. Monitoring of the animals was followed by individual coprological examinations and slaughter of the animals 15 days after treatment to collect and count flukes from the liver. Efficacy was measured as the reduction in the percentage of flukes of treated animals relative to untreated controls. Results indicated an efficacy of 80.0, 43.8, and 100% for 8-week-old flukes and 62.1, 57.9, and 100% for 4-week-old flukes in the three experimental groups, respectively. Even though guanabenz acetate showed a high efficacy, it was highly toxic since two animals died approximately 24 h after being treated. We conclude that further investigations should be conducted to perform computer-aided prediction of drugs aimed to detect fasciolicide activity.

Synthesis and fasciolicidal activity of 5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole.

The synthesis and fasciolicidal activity of 5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole (6) is described. Compound 6 showed 100% activity in vitro at 146.70 and 29.34 microM concentrations. It also completely removed 3-d and 10-week-old Fasciola hepatica in sheep at a dose of 15 mg/kg.

Eficacia del 6-cloro-2metiltio-5-(1-naftiloxi) bencimidazol contra Fasiola hepatica de cuatro y diez semanas de edad en bovinos de México / Efficacy of 6-chloro-2-methiltio-5-(1-naphtiloxi) bencimidazole against 4 and 10 week-old Fasciola hepatica in cattle from Mexico

El objetivo del presente estudio fue evaluar la eficacia fasciolicida del 6-cloro-2- metiltio-5-(1-naftiloxi) bencimidazol denominado compuesto "alfa" contra fasciolas de cuatro y 10 semanas de edad en bovinos. Se utilizaron 15 novillos libres de infección por F. Hepática que se infectaron por vía oral con 300 metacercarias, administradas 150 en el día 0 y 150 en el día 45, respectivamente. A todos los bovinos se les tomaron muestras de heces con el propósito de corroborar la presencia del parásito mediante análisis coprológicos. El día 75, los grupos 1 y 2 fueron tratados con los compuestos alfa y triclabendazol a dosis única de 12 mg/kg, vía oral. El grupo 3 quedó como testigo sin tratamiento. A los 45 días postratamiento todos los bovinos fueron sacrificados para separar el hígado y cuantificar los vermes presentes. La eficacia se midió con base en el número de fasciolas presentes en los grupos tratados respecto del testigo. Los resultados indicaron una eficacia de 99.4 por ciento para el compuesto alfa y de 100 por ciento para el triclabendazol. Se concluye que el compuesto alfa mostró alta eficacia contra fasciolas de cuatro y 10 semanas de edad.

Eficacia fasciolicida de dos compuestos de sintesis química in vitro e in vivo en ovinos / In vitro and in vivo fascioliscide efficacy of two chemical compounds in sheep

Se evaluó la eficacia fascioliscida del 6-cloro-5-(1-naphtoxy)-2-methyltiobencimidazol, denominado compuesto alfa, y del 6-cloro-5-(2-naphtoxy)-2-methyltiobencimidazol, denominado beta, bajo condiciones in vitro e in vivo. Para ambos compuestos la eficacia in vitro se evaluó a concentraciones de 50, 10, 3.33, 1.11 y 0.37 mg/L, utilizando metacercarias de Fasciola hepática desenquistadas. La eficacia se determinó con base en la sobrevivencia de estos cuatro días posexposición a los químicos. El compuesto alfa mostró una eficacia de 100 por ciento, 100 por ciento, 77.5 por ciento, 0.0 por ciento y 0.0 por ciento y el compuesto beta de 100 por ciento, 67.5 por ciento, 1.75 por ciento, 0.0 por ciento y 0.0 por ciento, respectivamente. Para la evaluación in vivo, se utilizaron 45 ovinos criollos, los cuales fueron infectados cada uno con 150 metacercarias de Fasciola hepática. Dos meses después, cuando todos lo ovinos se diagnosticaron positivios a los huevos del parásito mediante la prueba de sedimentación, los borregos se subdividieron en 5 grupos de 9 animales cada uno. Los grupos 1 y 2 fueron tratados con 10 y 15 mg/kg/vía oral del producto alfa, respectivamente. Los grupos 3 y 4 fueron dosificados con 10 y 15 mg/kg/vía oral del compuesto beta, respectivamente. El grupo 5 fungió como testigo sin tratamiento. Quince días posteriores al tratamiento, los ovinos se sacrificaron para colectar y cuantificar las fasciolas en el hígado. La eficacia fue determinada como porcentaje de reducción de fasciolas en los grupos tratados con respecto al testigo. Los resultados indicaron una eficacia de 80.6 y 86.9 por ciento para los grupos 1 y 2, respectivamente, y de 0.0 por ciento para los grupos 3 y 4, respectivamente. Mediciones de la longitud de fasciolas y peso del hígado, no mostraron algún efecto adverso atribuible a los tratamientos. Se concluye que el compuesto alfa bajo condiciones in vitro e in vivo, mostró una eficacia fasciolicida altamente promisoria y el compuesto beta solamente eficacia aceptable en el escrutinio in vitro

Eficacia fasciolicida del compuesto"alfa" contra estadios juveniles y adultos en ovinos / Fascioliscide efficacy of compound alfa againts juvenile and adult stages in sheep

Se evaluó la actividad fasciolicida del 6-cloro-5-(l-naphtoxy)-2-methyltiobencimidazol, denominado compuesto alfa, contra fasciolas de 4 y 8 semanas de edad en ovinos. Se utilizaron 50 ovinos criollos, los cuales se infectaron oralmente con 200 metacercarias de F. hepática. Cuatro semanas después de la infección, todos los ovinos fueron reinfectados cada uno con otras 200 metacercarias. Ocho semanas después a la infección inicial, cuando todos los animales estaban positivos a huevos del parásito, fueron divididos al azar en 5 grupos de 10 animales cada uno. Los grupos 1 al 4, fueron tratados oralmente con el compuesto a una dosis de 10, 15, 22.2 y 30 mg/kg de peso corporal, respectivamente. El grupo 5 permaneció como testigo sin tratamiento. Dos días después del tratamiento, todos los ovinos fueron sacrificados con el fin de colectar y contar las fasciolas presentes en el hígado. La eficacia se determinó como porcentaje de reducción de fasciolas en los grupos tratados, en comparación con el testigo. Los reusltados mostraron que a dosis de 10, 15, 22.2 y 30 mg/kg de peso vivo, el compuesto alfa removió fasciolas de 4 semanas de edad en un 82.2 por ciento, 87.2 por ciento, 90.8 por ciento y 94.3 por ciento y fasciolas de 8 semanas en 81.7 por ciento, 88.1 por ciento, 87.2 por ciento y 90.0 por ciento, respectivamente. La eficacia promedio para ambos estadios de 4 y 8 semanas fue de 82.0 por ciento, 87.6 por ciento, 89.2 y 92.4 por ciento, para las respectivas concentraciones concluye que la eficacia fasciolicida, conferida por el compuesto alfa a las dosis administradas, fue moderadamente aceptable, siendo las dosis de 15 mg/kg la más idónea

Eficacia de un compuesto experimental contra Fasciola hepática juvenil y adulta en ganado ovino / Efficacy of un experimental compound againts juvenile and adult Gasciola hepatica in sheep

Se evaluó la eficacia fasciolicida del 2-amino-5 (6)-cloro-1-metoxicarbonil bencimidazol denominado compuesto "A", contra fasciolas de cuatro y ocho semanas de edad en ganado ovino. Se utilzaron 20 ovinos machos criollos, entre 8 y 12 meses de edad, los cuales fueron infectados por vía oral con 150 metacercarias de F. hepatica por animal. En la semana cuatro, todos los animales fueron rinfectados con 150 metacercarias más. Ocho semanas después, lo ovinos positivos a eliminación de huevos del parásito, fueron divididos al azar en 4 grupos de 5 animales cada uno. Los grupos 1, 2 y 3 se trataron con el compuesto "A" por vía oral con 5, 10 y 15 mg/kg de peso, respectivamante. El grupo 4 fue testigo sin tratamiento. A las dos semanas posteriormente, los ovinos se sacrificaron y se cuantificaron las fasciolas en hígado. La eficacia se determinó con base en el porcentaje de reducción de fasciolas. Los resultados mostraron que a las dosis de 5, 10 y 15 mg/kg de peso vivo, el compuesto "A" removió fasciolas de cuatro semanas de edad, en 58.6 por ciento, 66.0 por ciento y 66.0 por ciento y fasciolas de ocho semanas en 24.8 por ciento, 46.0 por ciento y 62.2 por ciento, respectivamante, generando un porcentaje global de eficacia de 35.7, 52.4 por ciento y 63.4 por ciento, respectivamante. Se concluye que la eficacia conferida por el compuesto "A" no es aceptable en términos de eficiencia fasciolicida