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Evaluation of mebendazole used concurrently with piperazine monohydrochloride in horses.

Forty horses from a herd known to have benzimidazole-resistant small strongyles were treated with mebendazole (8.8 mg/kg) or combinations of mebendazole and piperazine monohydrochloride (25, 40, or 55 mg of piperazine base/kg). Pretreatment and 7-day posttreatment fecal examinations were done. Fecal cultures and strongyle egg per gram (epg) counts, and in vitro testing for benzimidazole resistance were performed. Results of fecal examinations prior to treatment were similar in all horses, and results of testing were positive for benzimidazole resistance. Horses treated with mebendazole and piperazine at all dosages had much lower geometric mean strongyle epg counts (2 to 4) and greater percentage reduction in geometric mean strongyle epg counts (99.7 to 99.9) at 7 days after treatment, compared with those measurements for horses treated with mebendazole alone. Adverse reactions to treatment were not observed.

Animals↗

Comparative anthelmintic efficacy of two schedules of mebendazole treatment in dogs.

Two schedules of anthelmintic oral treatment, using mebendazole powder, were compared in 73 dogs naturally infected with common helminth intestinal parasites. Mebendazole powder was administered to 26 dogs at doses of 22 mg/kg once daily for 3 days and was compared with the same dose given only daily for 5 days into 23 dogs. The 24 other dogs were kept as controls and received a placebo treatment for 5 days. Efficacy results for the 3-day treatment schedule of mebendazole were as follows: Toxocara canis, 100%; Uncinaria stenocephala, 100%; Ancylostoma caninum, 99.4%; Trichuris vulpis, 100%; and Taenia pisiformis, 93.9%. Mebendazole powder given on the 5-day treatment schedule was 100% efficacious against the foregoing parasites. Anthelmintic efficacy against Dipylidium caninum was not detected in either schedule of treatment.

Administration, Oral↗

Interaction of mebendazole with tubulin from body wall muscle, intestine, and reproductive system of Ascaris suum.

The binding of tritiated mebendazole, a benzimidazole anthelmintic, to tubulin derived from intestine, body wall muscle, and reproductive system of adult Ascaris suum was examined and compared. Mebendazole binding was resolved into specific and nonspecific binding and the binding affinity (Ka) and maximum binding at infinite ligand concentration (Bmax) determined. Electron microscopy was performed to assess the tubulin in various tissues of A. suum quantitatively by observing the presence of microtubules. Total binding was highest in intestine followed by body wall muscle. It was least in the reproductive system. The intestine demonstrated greater specific binding per milligram of protein than the body wall muscle. However, in the reproductive system extract, high affinity binding was not detected. After correction for nonspecific binding of ligand, the results indicated that the Bmax of mebendazole for the tubulin of A. suum intestine was about 3-fold higher than for that of body wall muscle. The Ka of mebendazole for intestinal tubulin was similar to that for body wall muscle. Electron microscopy of A. suum tissues demonstrated that the tubulin content decreased from the intestine through the body wall muscle to the reproductive system. Differences in tubulin content from different tissues may determine the selective sensitivity of these tissues to benzimidazole attack.

Animals↗

[The efficacy of mebendazole and praziquantel on larval taeniids from mouse, rabbit and pig (author's transl)].

The efficacy of Mebendazole (Janssen) and Praziquantel (Bayer) on Cysticercus fasciolaris, C. tenuicollis resp. C. pisiformis was studied in 125 mice, 63 pigs and 30 rabbits. All mice were infected naturally with C. fasciolaris. The pigs were infected experimentally with 2000 resp. 5000 eggs of Taenia hydatigena and the rabbits with 1500 eggs of Taenia pisiformis. 8 weeks p.i. animals were divided into groups and received 25 mg/kg Mebendazole or 50 mg/kg Praziquantel on 5 consecutive days as well as 5 mg/kg Mebandazole resp. 10 mg/kg praziquantel for 14 days. The applied doses of 62.5 and 12.5 mg/kg Mebendazole to mice for 10 days or 14 days showed almost no efficacy against C. fasciolaris whereas 250 and 125 mg/kg Praziquantel given for 10 days gave 100% good results. We found that Mebendazole is highly efficient only against C. tenuicollis at a concentration of 25 mg/kg in the pig, whereas in the rabbit the 5 mg dose over 14 days still revealed good results. Praziquantel showed a virtually 100% success using 50 mg/kg for 5 days and 10 mg/kg for 14 days, whereas the efficacy of Praziquantel against C. pisiformis in rabbits administering the same dose was not satisfying.

Animals↗

Studies on the effect of fenbendazole and mebendazole on some enzymes of swine kidney worm Stephanurus dentatus.

The effect of fenbendazole and mebendazole on the activity of some enzymes of the homogenates of swine kidney worm Stephanurus dentatus was investigated. Fenbendazole at 10(-5) M inhibited malate oxidation by 49% and 51% and oxaloacetate reduction by 33% and 40% whereas, mebendazole at 10(-5) M diminished malate oxidation by 25% and 35% and oxaloacetate reduction by 12% and 14% in male and female S. dentatus, respectively. Lactate dehydrogenase activity was inhibited by 45% and 50% in male and female worm respectively by 10(-5) M fenbendazole. Aldolase activity in both male and female S. dentatus was inhibited by 10(-5) M fenbendazole and mebendazole. Fenbendazole at 10(-5) M caused moderate inhibition of acid and alkaline phosphomonoesterases but mebendazole did not show a significant effect on these enzymes. Cholinesterase activity was not affected significantly with either compound. The possible mode of action of the two compounds is compared.

Alcohol Oxidoreductases↗

Studies on efficacy of praziquantel and mebendazole-medicated salt in treatment of Echinochasmus fujianensis infection.

The therapeutic effect of praziquantel and mebendazole-medicated salt has been studied in 109 cases with Echinochasmus fujianensis infection. These cases were randomly divided into four groups: 2 groups with a single dose of praziquantel 5 mg/kg or 2.5 mg/kg; and other 2 groups with mebendazole 800mg or 400 mg in 10d table salt. Four weeks after treatment, the egg negative conversion rates were 100%, 92.3%, 85.2% and 71.4% respectively, the egg reduction rates were 84.8-100%, and side-effects were mild. The symptoms caused by infection such as abdominal pain, diarrhea, distension and anorexia were obviously relieved. These data indicated that praziquantel is the drug of choice in the treatment of Echinochasmus fujianensis. The dosage is only 2.5 mg/kg, and its egg negative conversion rate and reduction rate reach 92.3% and 95.4%, respectively. For convenience, the dosage can be made according to their age. Children under 12 take half a tablet (100 mg), and one tablet (200 mg) for those over 12. This dosage is approximately equal to 2.5-5.0 mg/kg. Although the efficacy of mebendazole is lower than praziquantel, its egg negative conversion rate also reaches 71.4-85%. Mebendazole-medicated salt can be used for treating Echinochasmus fujianensis infection as the presence of co-infection with nematodes.

Adolescent↗

Persistent Strongyloides stercoralis in a blind loop of the bowel. Successful treatment with mebendazole.

Three courses of thiabendazole therapy, including one course given directly into a blind loop of the bowel, failed to eradicate Strongyloides stercoralis from a 55-year-old man who had undergone a Roux-en-Y operation. The patient responded to 1.5 g/day of mebendazole for 14 days, and the infection did not recur. Our case illustrates the difficulty of eliminating S stercoralis from a blind loop of the bowel and indicates that mebendazole therapy used in adequate doses is effective treatment for strongyloidiasis. The lack of toxicity of mebendazole makes it a desirable drug for Strongyloides infestation resistant to thiabendazole therapy.

Benzimidazoles↗

Fasciola hepatica: mebendazole and thiabendazole pharmacokinetics in sheep.

Pharmacokinetics of the two anthelmintic drugs mebendazole and thiabendazole were determined in sheep before and 4, 8, 13, 19, and 25 weeks after an infestation of animals by an oral administration of 150 metacercariae of Fasciola hepatica. The parasitic pathology was ascertained by the increase in plasma enzyme activities of glutamate dehydrogenase and gamma-glutamyltransferase. After oral administration of mebendazole (25 mg.kg-1), the parent drug and especially its reduced metabolite were present in plasma of animals. A significant 1.5- to 2.7-fold increase in the mean residence time occurred by Weeks 13 to 25 postinfection. This change was related to decreases in both the elimination from the pharmacokinetic compartment representing the reduced metabolite and the area under the curve of plasma metabolite concentration versus time. A 59% decrease in MBZ reduction was demonstrated in liver microsomes prepared from 12-week-infected sheep. This reductase activity was characterized by NADPH dependency and a pH peak activity of 6.0 and was competitively inhibited by daunomycin. In sheep receiving a 50 mg.kg-1 oral dose of thiabendazole, fascioliasis provoked only decreased plasma concentrations of the metabolite 5-hydroxythiabendazole by Weeks 4 to 25 postinfection. This change parallels an increase in urinary excretion of free metabolite but this is of minor significance in the general fate of the drug because of the prevalence of excretion as conjugates. In summary, fascioliasis appears to have more of an effect on the pharmacokinetics of mebendazole, a drug intensively metabolized by the liver into a metabolite present at high concentrations in the plasma of animals and humans.

Administration, Oral↗

Plasma concentrations of mebendazole during treatment of echinococcosis: preliminary results.

High oral doses of mebendazole are used experimentally for the treatment of human alveolar and cystic echinococcosis. In order to assess bioavailability of this drug 1.5 g doses were given to 3 volunteers. Measurable plasma concentrations of 17 to 134 nmol/l were found only if mebendazole was given together with a fatty meal. In a patient with cholestasis plasma concentrations were higher than in the 3 normal subjects. In patients on long term treatment the increase in plasma concentration after administration of a 1 g dose varied between 0 and 500 nmol/l. It is concluded that systemic availability of mebendazole is enhanced by concomitant food intake. In view of the large intra- and interindividual variation in plasma concentration, monitoring plasma levels during long term therapy appears advisable.

Administration, Oral↗

Differential efficacy of mebendazole and albendazole against Necator americanus but not for Trichuris trichiura infestations.

The effect of single oral doses of albendazole 600 mg and mebendazole 1 g given to 56 and 60 men, respectively, with T. trichiura and/or N. americanus infestation has been studied. Both albendazole and mebendazole cured more than 90% of T. trichiura infestations, but only albendazole (95%) and not mebendazole (21%) had a high cure rate for N. americanus infestations. Thus, albendazole is the preferred benzimidazole derivate for the mass treatment of subjects with T. trichiura and/or N. americanus infestations.

Albendazole↗

Identification of biliary metabolites of mebendazole in the rat.

Three metabolites of mebendazole were isolated from the bile of rats dosed with a mixture of mebendazole and pentadeuteromebendazole. The identification was based upon the appearance of the characteristic doublet in the mass spectrum of the compounds and the comparison of their fragmentations with those of authentic compounds. Cochromatography of the metabolites with the authentic compounds on HPLC supported the identification. Methyl-5(6)-(alpha-hydroxybenzyl)-2-benzimidazole carbamate, 2-amino-5(6)-(alpha-hydroxybenzyl) benzimidazole and 2-amino-5(6)-benzoylbenzimidazole were identified as metabolites after enzymic conjugate hydrolysis. Some unmetabolized mebendazole was also found.

Animals↗

Phenantroline, lovastatin, and mebendazole do not inhibit oviposition in the murine experimental infection with Angiostrongylus costaricensis.

Abdominal angiostrongyliasis is a zoonotic infection produced by a metastrongylid intra-arterial nematode, Angiostrongylus costaricensis. Human accidental infection may result in abdominal lesions. The presence of the eggs in the tissues plays an essential role in morbidity of abdominal angiostrongyliasis. The objective of this study is to evaluate and compare the effects of lovastatin, phenanthrolin, and mebendazole on oviposition of A. costaricensis in a murine experimental model. Each group of 12 male Swiss mice (Mus musculus) was orally infected with 10 L3 of the "Santa Rosa" strain of A. costaricensis. Two control groups were established: (1) mice were infected and not treated; (2) noninfected and nontreated animals. The experimental groups received (1) lovastatin TL), at a daily dose of 250 mg/kg for 10 consecutive days 16 days after infection; (2) phenanthroline at a daily dose of 20 mg/kg for 5 consecutive days 21 days after infection; and (3) mebendazole at a daily dose of 5 mg/kg for 5 consecutive days 21 days after infection. There was no significant inhibition of oviposition for lovastatin- and mebendazole-treated animals, whereas phenanthroline was associated with the lowest averages of larviposition per postinfection day and significant reduction of mortality.

Angiostrongylus↗

Treatment of fish parasites. 11. Effects of different benzimidazole derivatives (albendazole, mebendazole, fenbendazole) on Glugea anomala, Moniez, 1887 (Microsporidia): ultrastructural aspects and efficacy studies.

Three different benzimidazole derivatives, albendazole [methyl-5-(propylthio)-2-benzimidazolcarbamate], mebendazole (methyl-5-benzoyl-2-benzimidazolcarbamatic acid methyl ester), and fenbendazole [methyl-5-(phenylthio)-2-benzimidazolcarbamate] were tested in vivo against Glugea anomala parasitizing the connective tissue of sticklebacks (Gasterosteus aculeatus). Naturally infected sticklebacks were incubated in aerated plastic aquaria (10 1) at 22 degrees C in water containing 0, 1, 5, 10, or 50 micrograms of either albendazole, mebendazole or febendazole for 2 or 6 h. For intermittent treatment, 2 micrograms substance was administered three times for 6 h at intervals of 36 h. At the ultrastructural level, at all developmental stages of G. anomala there were no significant differences in the kind of damage caused by either albendazole, mebendazole, or febendazole. Starting with a dose of 1 microgram/ml for 2 h, each of the drugs irreversibly damaged uni- and multinucleate meronts, sporogonial plasmodia, and sporoblasts. Disorganized spores were also observed. Treatment with higher doses (10 micrograms/ml, 2 or 6 h) caused malformations of the merogonic and the sporogonic stages, a significant reduction in the number of ribosomes, and disruptions of the nuclear membranes. The first recognizable treatment effect was an enlargement of the smooth endoplasmic reticulum. In the sporogonial plasmodia, the membranes of the sporophorous vesicle envelopes were lumpy or even completely destroyed. After incubation with the highest dose (50 micrograms/ml, 6 h), microtubules were apparent within the karyoplasm of the uninucleate meronts. After interval treatment, all forms of damage were intensified, especially in the mature spores. When treatment was done three times at low doses (3 x 2 micrograms/ml, 6 h, 36-h intervals), spore infectivity was drastically lowered. Therefore, it seems likely that an intermittent regimen of medicinal baths can be successfully applied against susceptible Microsporidia in fish.

Albendazole↗

Experience with mebendazole in the treatment of inoperable hydatid disease in England.

Eleven heterogeneous patients with inoperable hydatid disease were treated with high doses of oral mebendazole, up to 200 mg/kg/day for 16 to 48 weeks. Toxicity was not encountered. Despite careful assessment it proved difficult critically to evaluate the efficacy of mebendazole. In four patients chemotherapy appeared to have been at least partially successful and success seems to have correlated with serum levels in excess of 100 ng/ml one to three hours after dosage. The problems of assessment are discussed and the need for controlled trials of mebendazole in hydatid disease are stressed.

Adolescent↗

In vivo 31P NMR spectrum of Hymenolepis diminuta and its change on short-term exposure to mebendazole.

The 31P NMR spectrum of the adult tapeworm, Hymenolepis diminuta, at 37 degrees C during perfusion with physiological saline was composed of 10 peaks. Based on chemical shifts and analysis of worm extracts, the phosphorus components included glucose-6-phosphate, fructose-6-phosphate, phosphorylcholine, glycerophosphoryl choline and -ethanolamine, nucleotide monophosphate-diphosphate and -triphosphate, nicotinamide adenine dinucleotide and uridine diphosphate glucose. The mean level of nucleotide triphosphate was 0.86 nmol (mg fresh weight)-1 and the nucleotide triphosphate/-diphosphate ratio 3.9. Based on the nucleotide triphosphate level, worms were viable for at least 3 h and the intracellular pH was maintained constant at approximately 6.7. Short-term exposure to mebendazole perfused at 11 or 27 microM solubilized in physiological saline containing 0.5% Tween 80 or 0.1% dimethyl sulphoxide had little effect on the nucleotide triphosphate level. Some cytological changes, however, were evident following perfusion of mebendazole. In contrast, exposure to 2,4-dinitrophenol caused a rapid decline in nucleotide triphosphate level. It was concluded that mebendazole does not exert its primary effect on oxidative phosphorylation.

Animals↗

High-performance liquid chromatographic determination of the anthelmintic mebendazole in eel muscle tissue.

A simple high-performance liquid chromatographic method for the determination of mebendazole in eel muscle tissue was developed. It is applicable for concentrations of 10 micrograms/kg and higher. Muscle tissue was extracted with ethyl acetate, and the extract, after addition of hexane, was concentrated and cleaned up on a silica gel solid-phase extraction column. Mebendazole was eluted from the column with 3% acetic acid in methanol. The eluate, after reconstitution in the chromatographic mobile phase, was analysed on a LiChrosorb RP-8 column with acetonitrile-0.05 M ammonium phosphate buffer (pH 6.2) (3:7, v/v) as the mobile phase. Detection was performed at 311 nm. The average mebendazole recovery over the concentration range 10-5000 micrograms/kg eel muscle tissue was 72 +/- 6.4%. The calibration curve for spiked samples was linear throughout the range 10-10,000 micrograms/kg (r = 0.999).

Animals↗

Angiostrongylus cantonensis: apoptosis of inflammatory cells induced by treatment with mebendazole or/and interleukin 12 in mice.

Angiostrongylus cantonensis is the major cause of human eosinophilic meningoencephalitis. ICR mice were infected orally with 35 infective larvae and sacrificed at 4-14 days, 25 days or 32 days post infection (dpi) for pathological and immunocytochemical examinations. In the non-treated group, no apoptosis signal was found in the meninges or parenchyma of the brains (4-14 dpi). Only a few apoptotic cells were noticed at 25 dpi (3%) and 32 dpi (10%). In the groups, the animals were given a single dose of mebendazole (20 mg/kg, per os at various times) or injections of interleukin 12 (IL-12) (10 ng/daily, intraperitoneally), all the animals were sacrificed at 14 dpi; the number of apoptotic cells was increased (17-21%). In the group that received a single dose of mebendazole (4 dpi) in combination with IL-12 injections (4-13 dpi), mild meningitis was observed, and most of the infiltrated inflammatory cells were in the apoptotic program (55%). Taken together, apoptosis of the inflammatory cells (most were eosinophils) could be induced when the infected mice were treated with mebendazole or/and IL-12.

Adjuvants, Immunologic↗

Long-term mebendazole therapy may be parasitocidal in alveolar echinococcosis.

Long-term chemotherapy of human alveolar echinococcosis with benzimidazole compounds (mebendazole, albendazole) has been shown to be primarily parasitostatic, but its curative (parasitocidal) efficacy is debated. This article reports on a 67-year-old male patient with non-resectable alveolar echinococcosis of the liver who had been continuously treated for 13 years with mebendazole (approximately 45-48 mg/kg body weight per day) and who was closely monitored according to a specific protocol. At the age of 80 years the patient died of oesophageal variceal bleeding. During treatment the hepatic lesion had decreased markedly in size in association with progression of perifocal calcification. At autopsy, a well-demarcated, necrotic, partially calcified, parasite-induced lesion of the right liver lobe and secondary biliary cirrhosis were found. Remnants of parasite tissue obtained from the periphery of the lesion showed a small-cystic structure, but it was not viable, as evidenced by transplantation of tissue blocks to rodents. The case is suggestive for a parasitocidal efficacy of mebendazole treatment carried out for 13 years, and is discussed in context with conflicting literature data.

Aged↗