-
Acta Medica (Hradec Kralove) 2017Flubendazole is a widely used anthelmintic drug belonging to benzimidazole group. The molecular mechanism of action of flubendazole is based on its specific binding to... (Review)
Review
Flubendazole is a widely used anthelmintic drug belonging to benzimidazole group. The molecular mechanism of action of flubendazole is based on its specific binding to tubulin, which results in disruption of microtubule structure and function, and in the interference with the microtubule-mediated transport of secretory vesicles in absorptive tissues of helminths. The microtubule-disrupting properties of benzimidazole derivatives raised recently interest in these compounds as possible anti-cancer agents. In this minireview flubendazole effects towards selected human malignant cells including myeloma, leukemia, neuroblastoma, breast cancer, colorectal cancer and melanoma are discussed along with basic data on its pharmacokinetics, metabolism and toxicity.
Topics: Cell Survival; Cellular Senescence; Dose-Response Relationship, Drug; Humans; Leukemia; Mebendazole; Microtubules; Multiple Myeloma; Tubulin
PubMed: 28399389
DOI: 10.14712/18059694.2017.44 -
Transactions of the Royal Society of... 1987The effectiveness of mebendazole as a microfilaricide in patients with loiasis was studied. The drug regimen was 1 g twice daily for 21 days in adults. During and after... (Clinical Trial)
Clinical Trial
The effectiveness of mebendazole as a microfilaricide in patients with loiasis was studied. The drug regimen was 1 g twice daily for 21 days in adults. During and after treatment, the microfilarial density was unchanged. Therefore, mebendazole has no direct effect on the microfilarial density of Loa loa.
Topics: Clinical Trials as Topic; Filariasis; Humans; Loiasis; Mebendazole
PubMed: 3318018
DOI: 10.1016/0035-9203(87)90156-8 -
International Journal of Molecular... Jan 2022Flubendazole, belonging to benzimidazole, is a broad-spectrum insect repellent and has been repurposed as a promising anticancer drug. In recent years, many studies have... (Review)
Review
Flubendazole, belonging to benzimidazole, is a broad-spectrum insect repellent and has been repurposed as a promising anticancer drug. In recent years, many studies have shown that flubendazole plays an anti-tumor role in different types of cancers, including breast cancer, melanoma, prostate cancer, colorectal cancer, and lung cancer. Although the anti-tumor mechanism of flubendazole has been studied, it has not been fully understood. In this review, we summarized the recent studies regarding the anti-tumor effects of flubendazole in different types of cancers and analyzed the related mechanisms, in order to provide the theoretical reference for further studies in the future.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; Cell Survival; Clinical Studies as Topic; Drug Evaluation, Preclinical; Drug Monitoring; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Mebendazole; Neoplasms; Organ Specificity; Signal Transduction; Treatment Outcome; Xenograft Model Antitumor Assays
PubMed: 35008943
DOI: 10.3390/ijms23010519 -
Journal of Chemotherapy (Florence,... Oct 1989The Authors report their personal experience in the treatment of 70 patients with hydatid cysts of different localization with mebendazole, following protocols approved...
The Authors report their personal experience in the treatment of 70 patients with hydatid cysts of different localization with mebendazole, following protocols approved by WHO. During treatment patients were submitted to careful clinical, biochemical, radiological and immunological controls. On the whole, 150 hydatid cysts and 13 cases of widespread hydatidosis were observed. Follow-up ranged from 6 months to 5 years. Morphological and/or volumetric modifications were observed in 64.3% of the total number of cysts treated, regardless of their localization. 9 relapses were observed, and all but one case showed the same previous sensitivity to a further cycle of mebendazole. The observed side effects were not severe.
Topics: Adolescent; Adult; Aged; Child; Echinococcosis; Female; Follow-Up Studies; Humans; Male; Mebendazole; Middle Aged; World Health Organization
PubMed: 2585032
DOI: 10.1080/1120009x.1989.11738914 -
European Journal of Clinical... 1983The biliary excretion of mebendazole has been investigated in two patients to whom it was given for the treatment of echinococcosis, although it was found to be only...
The biliary excretion of mebendazole has been investigated in two patients to whom it was given for the treatment of echinococcosis, although it was found to be only partly effective. Oral mebendazole was extensively metabolized and the conjugated parent substance and its metabolites were excreted in the bile. One patient without cholestasis and with normal liver function had an apparent total biliary clearance (776 ml/min) which approached the hepatic plasma flow. The other patient with cholestasis and impairment of the hepatic drug metabolizing capacity showed a drastically reduced apparent total biliary clearance of 3.8 ml/min. The average plasma level of mebendazole was significantly lower in the former and higher in the latter patient (0.06 and 0.91 nmol/ml, respectively). The data suggest that impaired metabolism and/or biliary elimination can account for the higher plasma mebendazole level in patients with liver damage.
Topics: Adult; Benzimidazoles; Bile; Biotransformation; Echinococcosis, Hepatic; Female; Humans; Liver Function Tests; Mebendazole; Middle Aged
PubMed: 6617730
DOI: 10.1007/BF00544020 -
Journal of Pharmaceutical and... Apr 2011In the present study, extraction of mebendazole across a supported-liquid membrane (SLM) was performed based on two different driving forces: (1) pH gradient over the...
In the present study, extraction of mebendazole across a supported-liquid membrane (SLM) was performed based on two different driving forces: (1) pH gradient over the SLM, and (2) electrical field sustained over the SLM. The extracted drug concentration was studied using reversed-phase HPLC-UV. At passive extraction conditions, mebendazole was extracted from alkaline samples (0.01 mmol L(-1) NaOH) into 1-undecanol immobilized in the pores of a porous hollow fiber of polypropylene (SLM), and then transported into 25 μL of 100mM HCl as the acceptor solution. Under electrokinetic migration conditions, mebendazole transported under applied voltage from acidic solutions (100 mmol L(-1) HCl) through 2-nitrophenyl octyl ether (NPOE) immobilized in the pores of hollow fiber, into 25 μL of 100 mmol L(-1) HCl as the acceptor solution. The effects of several factors including the nature of organic solvent, pH of donor and acceptor solutions, extraction time and stirring speed on the extraction efficiency of the drug were investigated and optimized. Under optimal conditions, preconcentration factors (PF) of 211 and 190 were obtained for the drug based on passive transport and electromembrane extraction (EME), respectively. Also, linear range of 0.5-1000 μg L(-1) with estimation of coefficient higher than 0.994 was obtained for both of the proposed methods. The results showed that EME has higher speed in comparison with simple passive transport. The methods were successfully applied to extract mebendazole from plasma and urine samples and satisfactory results were obtained.
Topics: Anthelmintics; Chemical Fractionation; Chromatography, High Pressure Liquid; Electrochemical Techniques; Humans; Hydrogen-Ion Concentration; Mebendazole; Membranes, Artificial; Microfluidic Analytical Techniques; Reference Standards; Solvents
PubMed: 21211924
DOI: 10.1016/j.jpba.2010.12.006 -
The American Journal of Tropical... Sep 1983Prolonged oral high-dose mebendazole therapy provided an effective anthelmintic regimen for trichinosis unresponsive to steroid therapy in one patient. Side effects were...
Prolonged oral high-dose mebendazole therapy provided an effective anthelmintic regimen for trichinosis unresponsive to steroid therapy in one patient. Side effects were limited to a Herxheimer-like reaction. Serum mebendazole levels documented gastrointestinal absorption. Repeat muscle biopsies and fluorescein angiography substantiated objective improvement.
Topics: Administration, Oral; Benzimidazoles; Electromyography; Female; Humans; Mebendazole; Middle Aged; Muscles; Trichinella; Trichinellosis
PubMed: 6625077
DOI: 10.4269/ajtmh.1983.32.980 -
Journal of the American Veterinary... Jul 1983The effect of repeated and exaggerated mebendazole administration was evaluated in dogs with and without experimentally induced altered liver function. Irish Setters and...
The effect of repeated and exaggerated mebendazole administration was evaluated in dogs with and without experimentally induced altered liver function. Irish Setters and Toy Poodles were dosed at 1, 3, and 5 times the therapeutic dose (22 mg/kg) of mebendazole for 17 days, without any effect on the liver. Mixed breed dogs that received increasing doses of mebendazole at 11 to 110 times the therapeutic dose for 2 months did not show adverse effects and remained in good health throughout the experiment. There was not substantial evidence that carbon tetrachloride-induced liver changes were exacerbated by subsequent repeated treatments with mebendazole at 15 times the therapeutic dose. Additionally, in dogs whose liver function was compromised experimentally by glutathione depletion and microsomal enzyme induction, administration of mebendazole at this same dosage for 30 days did not result in any hepatotoxic effect. When mebendazole was given at 15 times the therapeutic dose prior to an hypoxic episode in dogs pretreated with a barbiturate and high protein diet, there was no evidence of any adverse effect on liver function. These metabolic manipulations, in conjunction with mebendazole administration, failed to reveal any mechanism of hepatic dysfunction associated with mebendazole treatment. Unrecognized factors appear to be involved with the rare cases of hepatic dysfunction that have been reported after mebendazole administration. Only careful documentation of field cases and further laboratory research can identify these factors.
Topics: Animals; Benzimidazoles; Chemical and Drug Induced Liver Injury; Dog Diseases; Dogs; Drug Evaluation; Female; Liver; Liver Diseases; Male; Mebendazole; Rats; Rodent Diseases
PubMed: 6874531
DOI: No ID Found -
Bioorganic & Medicinal Chemistry Oct 2003Albendazole (Abz) and Mebendazole (Mbz) analogues have been synthesized and in vitro tested against the protozoa Giardia lamblia, Trichomonas vaginalis and the helminths... (Comparative Study)
Comparative Study
Albendazole (Abz) and Mebendazole (Mbz) analogues have been synthesized and in vitro tested against the protozoa Giardia lamblia, Trichomonas vaginalis and the helminths Trichinella spiralis and Caenorhabditis elegans. Results indicate that compounds 4a, 4b (Abz analogues), 12b and 20 (Mbz analogues) are as active as antiprotozoal agents as Metronidazole against G. lamblia. Compound 9 was 58 times more active than Abz against T. vaginalis. Compounds 8 and 4a also shown high activity against this protozoan. Compounds 4b and 5a were as active as Abz. None of the Mbz analogues showed activity against T. vaginalis. The anthelmintic activity presented by these compounds was poor.
Topics: Albendazole; Animals; Antiparasitic Agents; Caenorhabditis elegans; Giardia lamblia; Mebendazole; Metronidazole
PubMed: 14527558
DOI: 10.1016/s0968-0896(03)00497-8 -
Journal of Neurotrauma Sep 2019We previously reported the serendipitous observation that fenbendazole, a benzimidazole anthelmintic, improved functional and pathological outcomes following thoracic...
We previously reported the serendipitous observation that fenbendazole, a benzimidazole anthelmintic, improved functional and pathological outcomes following thoracic spinal cord contusion injury in mice when administered pre-injury. Fenbendazole is widely used in veterinary medicine. However, it is not approved for human use and it was uncertain if only post-injury administration would offer similar benefits. In the present study we evaluated post-injury administration of a closely related, human anthelmintic drug, flubendazole, using a rat spinal cord contusion injury model. Flubendazole, administered i.p. 5 or 10 mg/kg day, beginning 3 h post-injury and daily thereafter for 2 or 4 weeks, resulted in improved locomotor function after contusion spinal cord injury (SCI) compared with vehicle-treated controls. Histological analysis of spinal cord sections showed that such treatment with flubendazole also reduced lesion volume and improved total tissue sparing, white matter sparing, and gray matter sparing. Flubendazole inhibited the activation of glial fibrillary acidic protein (GFAP); suppressed cyclin B1 expression and Bruton tyrosine kinase activation, markers of B cell activation/proliferation and inflammation; and reduced B cell autoimmune response. Together, these results suggest the use of the benzimidazole anthelmintic flubendazole as a potential therapeutic for SCI.
Topics: Animals; Antinematodal Agents; Drug Repositioning; Female; Mebendazole; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries
PubMed: 30747048
DOI: 10.1089/neu.2018.6160