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Scientific Reports Apr 2021Mebendazole is used extensively for treatment of local gut helminthic and invasive echinococcus infections. Anticancer effects of mebendazole have been shown in...
Mebendazole is used extensively for treatment of local gut helminthic and invasive echinococcus infections. Anticancer effects of mebendazole have been shown in experimental cancer models and in case studies in patients with advanced cancer. Given these observations, the aims of this study were to investigate safety and efficacy of individualized dosed mebendazole in the cancer indication. Patients with treatment refractory gastrointestinal cancer were treated with individualized dose adjusted mebendazole up to 4 g/day to target a serum concentration of 300 ng/ml. Efficacy and safety were assessed by CT-scans, clinical surveillance and blood sampling. Eleven patients were included in the study and 10 started the treatment phase. Two patients stopped treatment prior to and the remaining eight after tumour evaluation by CT-scan at 8 weeks, all due to progressive disease. Four patients also fulfilled criteria suggested for hyperprogression. Only five patients reached the target serum-mebendazole concentration. No severe adverse effects were observed. Individualized dose adjusted mebendazole is safe and well tolerated in patients with advanced cancer but all patients experienced rapid progressive disease. New approaches such as prodrug development and combination with other anticancer drugs seem needed for further exploration of mebendazole as an anticancer drug.
Topics: Adult; Aged; Antineoplastic Agents; Female; Gastrointestinal Neoplasms; Humans; Male; Mebendazole; Middle Aged; Tomography, X-Ray Computed
PubMed: 33903692
DOI: 10.1038/s41598-021-88433-y -
British Journal of Clinical Pharmacology Sep 1987In eight patients (five with peptic ulcer disease and three with hydatid cysts), the [14C]-aminopyrine breath test (ABT) and maximum serum concentration of mebendazole...
In eight patients (five with peptic ulcer disease and three with hydatid cysts), the [14C]-aminopyrine breath test (ABT) and maximum serum concentration of mebendazole following a dose of 1.5 g of mebendazole three times daily were determined before and after treatment with cimetidine (400 mg three times daily for 30 days). Serum mebendazole concentrations were measured in blood samples taken 2 h after each drug intake. Cimetidine lowered the 14CO2 specific activity (SA) at 1 h (P less than 0.01) and increased the maximum serum concentration of mebendazole (P less than 0.01). A significant correlation was found between SA at 1 h and the highest concentration of mebendazole before (r = -0.71, P less than 0.05) and after (r = -0.82, P less than 0.05) cimetidine ingestion. Combined administration of cimetidine and mebendazole resulted in the complete resolution of previously unresponsive hydatid cysts.
Topics: Adult; Aminopyrine; Breath Tests; Cimetidine; Drug Interactions; Echinococcosis, Hepatic; Female; Humans; Male; Mebendazole; Middle Aged
PubMed: 3663452
DOI: 10.1111/j.1365-2125.1987.tb03186.x -
The American Journal of Tropical... Mar 1978Mebendazole (methyl-5-benzoylbenzimidazole-2-carbamate: Vermox), a broad spectrum anthelmintic, cured 22 (88%) children with symptomatic trichuriasis when given as a...
Mebendazole (methyl-5-benzoylbenzimidazole-2-carbamate: Vermox), a broad spectrum anthelmintic, cured 22 (88%) children with symptomatic trichuriasis when given as a single 6-day course in a dosage of 100 mg twice daily. A further 3 (12%) were cured after a repeat 6-day course of therapy. Thus complete parasite eradication was achieved in all. The administration of an antidiarrheal agent, loperamide hydrochloride (Imodium), appeared to enhance the efficacy of mebendazole. Both drugs were well tolerated and completely free of any toxic effects.
Topics: Ascariasis; Benzimidazoles; Child; Child, Preschool; Drug Therapy, Combination; Humans; Infant; Loperamide; Mebendazole; Trichuriasis
PubMed: 646017
DOI: 10.4269/ajtmh.1978.27.255 -
European Journal of Pharmaceutical... Jan 2019Mebendazole (MBZ), designated as a WHO essential drug, can exist in diverse solid forms and presents low absorption at the gastrointestinal level. Considering the...
Mebendazole (MBZ), designated as a WHO essential drug, can exist in diverse solid forms and presents low absorption at the gastrointestinal level. Considering the potential of cyclodextrins to enhance the solubility and permeability of drugs, inclusion complexes of polymorphs A and C of MBZ with β‑cyclodextrin were obtained. The characterization of the complexes in solid state was performed by using a combination of experimental techniques including Fourier transform infrared spectroscopy, powder X-ray diffractometry and solid state nuclear magnetic resonance. Moreover, the effect of the binary complexes on their physical stability was evaluated. In addition, for a complete characterization of polymorphs A and C, one dimensional spectra and correlation nuclear magnetic resonance experiments were employed. Our physical studies showed that the inclusion complexes were new crystalline forms that induced shifts and broadening in the infrared and nuclear spectra. A molecular modelling analysis performed on the inclusion modes, demonstrated that the most favourable structure for the complex was the head down orientation. Moreover, the intermolecular interactions calculated for the complex with the atoms in molecules theory are in good agreement with the spectroscopic results. The inclusion complexes exhibited an increment of solubility in simulated physiological media. Furthermore, it was demonstrated that the complex formation did not affect the physical stability of the polymorphs.
Topics: Anthelmintics; Crystallization; Mebendazole; Models, Molecular; beta-Cyclodextrins
PubMed: 30445224
DOI: 10.1016/j.ejps.2018.11.012 -
The American Journal of Tropical... Nov 1975
Topics: Adolescent; Adult; Aged; Benzimidazoles; Capillaria; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Intestinal Diseases, Parasitic; Male; Mebendazole; Middle Aged; Nematode Infections; Philippines; Trichuroidea
PubMed: 1200258
DOI: 10.4269/ajtmh.1975.24.932 -
British Journal of Clinical Pharmacology Jan 1985Five volunteers, whose ages ranged between 37 and 64 years, took part in a crossover study to determine the pharmacokinetics and bioavailability of mebendazole in man...
Five volunteers, whose ages ranged between 37 and 64 years, took part in a crossover study to determine the pharmacokinetics and bioavailability of mebendazole in man following intravenous and oral administration of a tracer dose of [3H]-mebendazole. Following intravenous administration, the average distribution half-life, elimination half-life and rate of clearance were 0.20 h, 1.12 h, and 1.063 min respectively. After oral administration of the solution, the average elimination half-life was 0.93 h, the apparent rate of clearance was 0.846 l/min, the average time to peak plasma concentration was 0.42 h, and the bioavailability of mebendazole was 22%. Comparison of metabolite area under the plasma concentration vs time data from each route of administration indicates that absorption of mebendazole from the gastrointestinal tract at this dose level is almost complete. The low bioavailability observed following oral administration at this dose level is postulated to be due to high first pass elimination. Approximately half of the administered dose of radioactivity following intravenous and oral administration was detected in the urine, and the major unconjugated metabolite of mebendazole was found to be 2-amino-5(6) [alpha-hydroxybenzyl]benzimidazole (IV), not 2-amino-5(6)benzoylbenzimidazole (II), as previously reported.
Topics: Absorption; Administration, Oral; Adult; Benzimidazoles; Biological Availability; Female; Humans; Injections, Intravenous; Kinetics; Male; Mebendazole; Middle Aged; Tritium
PubMed: 3978023
DOI: 10.1111/j.1365-2125.1985.tb02616.x -
Clinical Cancer Research : An Official... Aug 2015Mebendazole (MBZ), first used as an antiparasitic drug, shows preclinical efficacy in models of glioblastoma and medulloblastoma. Three different mebendazole polymorphs...
PURPOSE
Mebendazole (MBZ), first used as an antiparasitic drug, shows preclinical efficacy in models of glioblastoma and medulloblastoma. Three different mebendazole polymorphs (A, B, and C) exist, and a detailed assessment of the brain penetration, pharmacokinetics, and antitumor properties of each individual mebendazole polymorph is necessary to improve mebendazole-based brain cancer therapy.
EXPERIMENTAL DESIGN AND RESULTS
In this study, various marketed and custom-formulated mebendazole tablets were analyzed for their polymorph content by IR spectroscopy and subsequently tested in an orthotopic GL261 mouse glioma model for efficacy and tolerability. The pharmacokinetics and brain concentration of mebendazole polymorphs and two main metabolites were analyzed by LC/MS. We found that polymorph B and C both increased survival in a GL261 glioma model, as B exhibited greater toxicity. Polymorph A showed no benefit. Polymorph B and C both reached concentrations in the brain that exceeded the IC₅₀ in GL261 cells 29-fold. In addition, polymorph C demonstrated an AUC₀₋₂₄h brain-to-plasma (B/P) ratio of 0.82, whereas B showed higher plasma AUC and lower B/P ratio. In contrast, polymorph A presented markedly lower levels in the plasma and brain. Furthermore, the combination with elacridar was able to significantly improve the efficacy of polymorph C in GL261 glioma and D425 medulloblastoma models in mice.
CONCLUSIONS
Among mebendazole polymorphs, C reaches therapeutically effective concentrations in the brain tissue and tumor with fewer side effects, and is the better choice for brain cancer therapy. Its efficacy can be further enhanced by combination with elacridar.
Topics: Animals; Brain Neoplasms; Chemistry, Pharmaceutical; Disease Models, Animal; Humans; Mebendazole; Medulloblastoma; Mice; Neoplasms, Experimental; Neutrophils
PubMed: 25862759
DOI: 10.1158/1078-0432.CCR-14-2681 -
The American Journal of Tropical... Apr 2007Vietnam is participating in a global de-worming effort that aims to treat 650 million school children regularly by 2010. The treatment used in Vietnam is single dose... (Randomized Controlled Trial)
Randomized Controlled Trial
Vietnam is participating in a global de-worming effort that aims to treat 650 million school children regularly by 2010. The treatment used in Vietnam is single dose oral mebendazole (Phardazone) 500 mg. We tested the efficacy of single dose mebendazole 500 mg in the therapy of hookworm infection in a randomized double-blind placebo-controlled trial among 271 Vietnamese schoolchildren. The treatment efficacy of single dose mebendazole in children did not differ significantly from placebo, with a reduction in mean eggs per gram of feces relative to placebo of 31% (95% CI -9 to 56%, P = 0.1). In light of these findings we then carried out a similar randomized trial comparing triple dose mebendazole, single dose albendazole, and triple dose albendazole against placebo in 209 adults in the same area. The estimated reduction in mean post-treatment eggs per gram of feces relative to placebo was 63% (95% CI 30-81%) for triple mebendazole, 75% (47-88%) for single albendazole, and 88% (58-97%) for triple albendazole. Our results suggest that single dose oral mebendazole has low efficacy against hookworm infection in Vietnam, and that it should be replaced by albendazole. These findings are of major public health relevance given the opportunity costs of treating entire populations with ineffective therapies. We recommend that efficacy of anti-helminth therapies is pilot tested before implementation of national gut worm control programs.
Topics: Adolescent; Adult; Aged; Albendazole; Animals; Anthelmintics; Child; Double-Blind Method; Female; Hookworm Infections; Humans; Male; Mebendazole; Middle Aged; Vietnam
PubMed: 17426180
DOI: No ID Found -
Journal of Nanobiotechnology Mar 2022Mebendazole (MBZ) is a well-known anti-parasite drug with significant anti-cancer properties. However, MBZ exhibits low solubility, limited absorption efficacy,...
Biodegradable and biocompatible subcutaneous implants consisted of pH-sensitive mebendazole-loaded/folic acid-targeted chitosan nanoparticles for murine triple-negative breast cancer treatment.
BACKGROUND
Mebendazole (MBZ) is a well-known anti-parasite drug with significant anti-cancer properties. However, MBZ exhibits low solubility, limited absorption efficacy, extensive first-pass effect, and low bioavailability. Therefore, multiple oral administration of high dose MBZ is required daily for achieving the therapeutic serum level which can cause severe side effects and patients' non-compliance.
METHOD
In the present study, MBZ-loaded/folic acid-targeted chitosan nanoparticles (CS-FA-MBZ) were synthesized, characterized, and used to form cylindrical subcutaneous implants for 4T1 triple-negative breast tumor (TNBC) treatment in BALB/c mice. The therapeutic efficacy of the CS-FA-MBZ implants was investigated after subcutaneous implantation in comparison with Control, MBZ (40 mg/kg, oral administration, twice a week for 2 weeks), and CS-FA implants, according to 4T1 tumors' growth progression, metastasis, and tumor-bearing mice survival time. Also, their biocompatibility was evaluated by blood biochemical analyzes and histopathological investigation of vital organs.
RESULTS
The CS-FA-MBZ implants were completely degraded 15 days after implantation and caused about 73.3%, 49.2%, 57.4% decrease in the mean tumors' volume in comparison with the Control (1050.5 ± 120.7 mm), MBZ (552.4 ± 76.1 mm), and CS-FA (658.3 ± 88.1 mm) groups, respectively. Average liver metastatic colonies' number per microscope field at the CS-FA-MBZ group (2.3 ± 0.7) was significantly (P < 0.05) lower than the Control (9.6 ± 1.7), MBZ (5.0 ± 1.5), and CS-FA (5.2 ± 1) groups. In addition, the CS-FA-MBZ treated mice exhibited about 52.1%, 27.3%, and 17% more survival days after the cancer cells injection in comparison with the Control, MBZ, and CS-FA groups, respectively. Moreover, the CS-FA-MBZ implants were completely biocompatible based on histopathology and blood biochemical analyzes.
CONCLUSION
Taking together, CS-FA-MBZ implants were completely biodegradable and biocompatible with high therapeutic efficacy in a murine TNBC model.
Topics: Animals; Chitosan; Folic Acid; Humans; Hydrogen-Ion Concentration; Mebendazole; Mice; Nanoparticles; Triple Negative Breast Neoplasms
PubMed: 35361226
DOI: 10.1186/s12951-022-01380-2 -
Archives of Disease in Childhood Apr 1991Thirty nine children with 71 hydatid cysts were given mebendazole orally in a dose of 100-200 mg/kg/day for 12 weeks and were followed up for a mean (SD) of 63 (24)... (Clinical Trial)
Clinical Trial
Thirty nine children with 71 hydatid cysts were given mebendazole orally in a dose of 100-200 mg/kg/day for 12 weeks and were followed up for a mean (SD) of 63 (24) months. Twenty children (three of them after a second course) were cured and another two avoided at least one operation. No serious side effects of the drug were observed.
Topics: Administration, Oral; Adolescent; Child; Child, Preschool; Drug Administration Schedule; Echinococcosis; Echinococcosis, Hepatic; Echinococcosis, Pulmonary; Female; Humans; Male; Mebendazole
PubMed: 2031617
DOI: 10.1136/adc.66.4.532