• 약학회지
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• 제20권1호
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• pp.27-31
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• 1976

The stability of a newly introduced anthelmintic, mebendazole, in sweetened and aqueous suspension was tested by the accelerated temperature method and the effect of pH on the stability of mebendazole was studied. Mebendazole in aqueous and sweetened suspension was very stable at the pH range from 4 to 8.

• Parasites, Hosts and Diseases
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• 제59권3호
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• pp.189-225
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• 2021

The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.117-125
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• 2019

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

• Biomolecules & Therapeutics
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• 제30권6호
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• pp.616-624
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• 2022

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC₅₀ of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC₅₀ of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.

• Parasites, Hosts and Diseases
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• 제32권1호
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• pp.49-52
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• 1994

1990년 4월부터 1992년 2월까지 인제대 부속 서울 백병원과 상계 백병원에 내원한 환자 중 대변에서 분선충(Strongwloides stercoralis)의 rhabditoid 유충 또는 기생세대 자충이 검출된 분선충 감염증 9례를 보고하고자 한다. 환자들은 50대와 70대 사이의 남자 7명 및 여자 2명으로 퇴행성 관절염으로 스테로이드계 약물을 장기 복용하였거나 소화기 장애, 고혈압, 간질환 정신장애 등 다양한 질환을 동반하고 있었다. 관절염, 소화기 장애 등으로 입원한 57세 여자 환자 1례에서는 albendazole 및 mebendazole 투여 4-5일 째의 설사변에서 분선충의 기생세대 자충 (parasitic females) 220마리가 회수되었다. 이 환자는 관절염에 대한 스테로이드 장기 복용으로 면역기능이 저하된 상태에서 자가감염된 중감염(hyperinfection) 예로서 우리 나라에서 기생세대 자충이 확인된 세 번째 증례이기도 하다.

• 약학회지
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• 제37권3호
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• pp.216-227
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• 1993

Complex formations of practically insoluble antelmintic drugs such as mebendazole (MBZ), albendazole (ABZ) and flubendazole (FBZ) with dimethyl-$\beta$-cyclodextrin (DM-$\beta$-CyD) and 2-hydroxypropyl-$\beta$-cyclodextrin (HP-$\beta$-CyD) together with $\alpha$-, $\beta$- and $\gamma$-cyclodextrins(CyDs) in duffered solutions were investigated by solubility method. $A_{L}$ type phase solubility diagrams were obtained in all cases except for the complexation (B$_{s}$, type) of FBZ with $\gamma$-CyD. The highest stability constants were obtained with DM-$\beta$-CyD, followed by $\alpha$-CyD > $\beta$-CyD > HP-$\beta$-CyD > $\gamma$-CyD for ABZ, and HP-$\beta$-CyD > $\gamma$-CyD > $\beta$-CyD > $\alpha$-CyD for FBZ at pH 1.2. On the other hand, solid dispersion systems of ABZ and FBZ with $\beta$- and DM-$\beta$-CyDs were prepared by solvent evaporation method and evaluated by dissolution, differential thermal analysis and powder x-ray diffractometry. The dissolution rates of ABZ- and FBZ-DM-$\beta$-CyD solid dispersions were much faster than those of drugs alone, corresponding physical mixtures and tablets on market both at pH 1.2 and 6.8. Although dissolution rates of all samples at pH 6.8 were by far lower than those obtained at pH 1.2, as explained by pH-solubility profiles for ABZ and FBZ, the dissolution rates at pH 6.8 of ABZ from $\beta$- and DM-$\beta$-CyD solid dispersions exceeded the respective equilibrium solubility (23.9 $\mu\textrm{g}$/ml). Fast dissolution of ABZ from solid dispersions with CyDs was attributed to the reduction of drug crystallinity and particle size which was supported by DTA and powder x-ray diffractometry. Consequently these results suggest that solid dispersion systems with CyDs may provide useful means to markedly enhance the solubility and dissolution of benzimidazole antelmintic drugs.

• Parasites, Hosts and Diseases
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• 제21권1호
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• pp.95-101
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• 1983

편층증의 개인치료와 집단관리에 있어서 메벤다졸의 유용성 및 효과를 측정하였다. 메벤다졸(100∼1,200mg) 투약 3주후 430명에 있어서의 치료효과는 15.0∼64.0% 및 24.6∼95.2%의 치유율 및 충란감소율을 보여 대체로 만족스럽지 못한 결과이었으나 메벤다졸의 총 투여량이 높으면 높을수록 치유율 및 충란감소율도 높아지는 것이 관찰되었다. 일정간격 반복투여(600mg용량)에 의한 집단관리를 주민(4개군, 총 551명)의 편충란양성율은 3개월간격(3일 분복군) 투여 군에서 가장 현저한 감소추세를 보여 관리시작후 1년만에 40.0%에서 5.6%로 저하되었고, 3개월 간격(단희 또는 2회 분복군), 6개월, 12개월군 및 대조군에서는 감소추세가 완만하거나 거의 관찰되지 않았다. 이상의 결과로 보아, 메벤다졸은 편충의 개인치료에는 그다지 우수한 결과를 나타내지 않았으나, 3개월간격으로 반복투여하면 집단관리에는 유효한 약제가 될 수 있을 것으로 생각되었다.

• 대한수의학회지
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• 제54권2호
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• pp.127-129
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• 2014

A male, 3.5 month old Pomeranian dog was diagnosed with a natural infection of Crenosoma (C.) vulpis in Daejeon, Korea. First stage larvae of C. vulpis were detected by fecal examination using the Baermann technique. Thoracic radiographs revealed mild, pervasive bronchial infiltration of the lung. Enumeration of larvae via the McMaster technique revealed 1,600 larvae per gram of feces. The dog was treated with mebendazole, and clinical symptoms were resolved 2 weeks post-treatment, as indicated by the subject presenting fecal tests negative for C. vulpis.

• Parasites, Hosts and Diseases
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• 제23권1호
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• pp.7-17
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• 1985

이 실험의 목적은 요충감염에 있어 감염 일자별 충체의 구충제 감수성, 특히 초기단계 충체의 감수성을 관찰하는 것이다. 이와함께 각 감염 일자별로 배출되는 충체의 발육상태를 관찰하여 감염기간별 발육 양상을 관찰하는 것도 이 실험의 또 다른 목적이다. 경기도 안양시 소재보육원 원아에서 살아있는 요중 암놈을 수집, 충란을 분리하고 부란기에서 3∼5일이 경과하여 유충이 형성된 충란을 약 500개섹 세었다. 이 실험의 대상으로 자원한 남자 19명 (17∼45세)에게 세어 놓은 충란을 투여하였다. 감염자는 '절란텍"치료군, "메벤다졸"치료군 및 대조군으로 나누었다. 각 치료군에 대해서는 감염후 4일, 8일, 16일, 20일, 24일, 28일, 32일 및 35일에 각 구충제를 투여하였다. 실험감염후 40일째 되는 날 대조군을 포함한 대상자 모두에게 '지르비늄"을 투여하여 감염을 완전히 중단시켰다. 카 약제 투여 후에는 그후 3일간의 대변을 수집하고 배출되는 요충충체를 수집하였다. 그 숫자를 세고, 충체의 발육정도를 관찰하였다. 그 결과를 요약하면 다음과 같다. 1. 이 실험에서 감염율은 대조군에서 0.6∼13. l%이었다. 감염 일자별로 수집한 충체의 발육단계가 모두 일정한 단계의 범위안에 있어 이번 실험에서 얻은 충체는 모두 실험감염의 결과 감염되어 발육한 충체라고 판단하였다. 2. "메벤다졸"을 감염후 4일, 8일, 16일에 투여한 예에서는 대조군에서 배출한 충체수의 37.5%, 2.5%, 및 67.5%가 40일째에 배출되 었다. 그 이후에 투약한 예에서는 투약 직후에는 충체가 배출되 었으나 감염 40일째에 투약한 후에는 충체배출을 하지 않았다. 3. '지란텔"을 감염후 4일, 8일, 16일, 24일, 28일, 32일 및 35일에 투여한 예에서는 대조군에서 배출한 충체수 의 90.7%, 25%, 45.5%, 8%, 2.7%, 5% 및 29.3%를 배출하고 있었다. 4. 배출된 충체는 모두 암놈이 었다. 충체의 길이는 일자별로 20일에서 40일째까지 일정한 양상으로 발육하고 있었고, 각 일자별, 증례별로 충체 길이는 정규분포 형식으로 분포하고 있었다. 이상의 소견에서 요충 암놈의 인체내 발육기간은 40일 이상이고 감염후 16일째까지의 어린 충체는"메벤다졸"이 나 "피란텔"에 대해서 정도의 차이는 있으나 치료에 저항한다고 결론을 내릴 수 있었다.

• Parasites, Hosts and Diseases
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• 제38권4호
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• pp.267-273
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• 2000

We report 5 cases of ocular toxocariasis in Korean adults complaining of visual impairment along with floating or bubbling sensation. Fundoscopic examination revealed a retinal detachment along with exudate in 4 cases. They all showed typical reaction by ELISA and immunoblot against Toxocra excretory-secretory antigen. One case showed high level of anti-Toxocara IgE antibodies (34.000 Toxocara units/L) as well as increased level of serum total IgE antibodies and the specific IgE antibodies for 3 inhalant antigens, suggesting that high level of anti-Toxocara IgE antibodies was associated with an atopic status. Clinical manifestations were improved after the sequential use of steroids then mebendazole. We also suggest that ocular toxocariasis should be thoroughly investigated even when an evocative uniocular inflammatory lesion is encountered in peripheral retina without a systematic disease.