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阿苯达唑和甲苯达唑作为抗寄生虫和抗癌药物:更新。

Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update.

机构信息

Institute of Parasitic Diseases, Korea Association of Health Promotion, Seoul 07649, Korea.

Department of Tropical Medicine and Parasitology, Seoul National University College of Medicine, Seoul 03080, Korea.

出版信息

Korean J Parasitol. 2021 Jun;59(3):189-225. doi: 10.3347/kjp.2021.59.3.189. Epub 2021 Jun 21.

Abstract

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.

摘要

阿苯达唑和甲苯咪唑(即苯并咪唑广谱驱虫药)在寄生虫感染和癌症治疗中的应用简要综述。这些药物已知可阻断寄生虫和哺乳动物细胞的微管系统,导致葡萄糖摄取和转运受阻,最终导致细胞死亡。最终,它们对寄生虫具有杀卵、杀幼虫和杀蠕虫作用,对宿主具有杀瘤作用。阿苯达唑和甲苯咪唑最常被开处方用于治疗肠道线虫感染(蛔虫病、钩虫感染、鞭虫病、旋毛虫病和蛲虫病),也可用于治疗肠道绦虫感染(带绦虫病和膜壳绦虫病)。然而,这些药物对组织线虫/绦虫感染(内脏、眼、神经和皮肤幼虫移行症、异尖线虫病、旋毛虫病、肝和肠毛细线虫病、血管圆线虫病、颚口线虫病、旋尾线虫病、麦地那龙线虫病、脑和皮下囊尾蚴病、棘球蚴病)也具有相当大的治疗效果。阿苯达唑还单独或与伊维菌素或乙胺嗪等其他药物联合用于治疗丝虫感染(淋巴丝虫病、盘尾丝虫病、罗阿丝虫病、曼森线虫病和犬弓蛔虫病)。阿苯达唑甚至被尝试用于治疗吸虫(片形吸虫病、华支睾吸虫病、后睾吸虫病和肠吸虫感染)和原生动物感染(贾第虫病、阴道毛滴虫病、隐孢子虫病和微孢子虫病)。这些药物通常安全,副作用少;然而,当它们被长期使用(>14-28 天)甚至仅使用 1 次时,可能会发生肝毒性和其他不良反应。在钩虫、鞭虫、可能的蛔虫、班氏丝虫和贾第虫中,已经出现了耐药性问题。特别值得注意的是,阿苯达唑和甲苯咪唑已被重新定位为有前途的抗癌药物。这些药物已被证明在体外和体内(动物)对肝癌、肺癌、卵巢癌、前列腺癌、结直肠癌、乳腺癌、头颈部癌症和黑色素瘤具有活性。两项关于阿苯达唑的临床报告和两项关于甲苯咪唑的病例报告显示了这些药物在不同类型癌症患者中的良好效果。然而,由于阿苯达唑的毒性,例如骨髓抑制引起的中性粒细胞减少,如果使用高剂量并长期使用,甲苯咪唑目前在抗癌临床试验中比阿苯达唑更受欢迎。

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