| 词条 | Mebendazole |
| 释义 |
| Watchedfields = changed | verifiedrevid = 457797273 | IUPAC_name =Methyl (5-benzoyl-1H-benzimidazol-2-yl)carbamate | image = Mebendazole.svg | width = 225 | tradename = Vermox[1] | Drugs.com = {{drugs.com|monograph|mebendazole}} | MedlinePlus = a682315 | pregnancy_AU = B3 | pregnancy_US = C | legal_AU = S2 | legal_CA = OTC | legal_UK = POM | legal_UK_comment = /P[2] | legal_US = Rx-only | routes_of_administration = By mouth | bioavailability = 2–10% | protein_bound = 95% | metabolism = Extensive liver | elimination_half-life = 3–6 hours | excretion = Faeces, urine (5–10%) | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 31431-39-7 | ATC_prefix = P02 | ATC_suffix = CA01 | ATC_supplemental = {{ATCvet|P52|AC09}} | PubChem = 4030 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00643 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 3890 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 81G6I5V05I | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00368 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 6704 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 685 | C=16 | H=13 | N=3 | O=3 | smiles = COC(=O)Nc3nc2ccc(C(=O)c1ccccc1)cc2[nH]3 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C16H13N3O3/c1-22-16(21)19-15-17-12-8-7-11(9-13(12)18-15)14(20)10-5-3-2-4-6-10/h2-9H,1H3,(H2,17,18,19,21) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = OPXLLQIJSORQAM-UHFFFAOYSA-N | melting_point = 288.5 }}Mebendazole (MBZ) is a medication used to treat a number of parasitic worm infestations.[3] This includes ascariasis, pinworm disease, hookworm infections, guinea worm infections, hydatid disease, and giardia, among others.[3] It is taken by mouth.[3] Mebendazole is usually well tolerated.[3] Common side effects include headache, vomiting, and ringing in the ears.[3] If used at large doses it may cause bone marrow suppression.[3] It is unclear if it is safe in pregnancy.[3] Mebendazole is a broad-spectrum antihelminthic agent of the benzimidazole type.[3] Mebendazole came into use in 1971, after it was developed by Janssen Pharmaceutica in Belgium.[4] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[5] Mebendazole is available as a generic medication.[6] The wholesale cost in the developing world is between 0.004 and 0.04 USD per dose.[7] In the United States a single dose is about 440.00 USD as of 2016, while in Australia and the UK it costs about 5 USD.[8] Medical useMebendazole is a highly effective, broad-spectrum antihelmintic indicated for the treatment of nematode infestations, including roundworm, hookworm, whipworm, threadworm, pinworm, and the intestinal form of trichinosis prior to its spread into the tissues beyond the digestive tract. Other drugs are used to treat worm infections outside the digestive tract, as mebendazole is poorly absorbed into the bloodstream.[9] Mebendazole is used alone in those with mild to moderate infestations. It kills parasites relatively slowly, and in those with very heavy infestations, it can cause some parasites to migrate out of the digestive system, leading to appendicitis, bile duct problems, or intestinal perforation. To avoid this, heavily infested patients may be treated with piperazine, either before or instead of mebendazole. Piperazine paralyses the parasites, causing them to pass in the feces.[10] It is also used rarely in the treatment of hydatid disease. Evidence for effectiveness for this disease, however, is poor.[11] Mebendazole and other benzimidazole antithelmetics are active against both larval and adult stages of nematodes, and in the cases of roundworm and whipworm, kill the eggs, as well. Paralysis and death of the parasites occurs slowly, and elimination in the feces may require several days.[9] Special populationsMebendazole is pregnancy category C, which means it has been shown to cause ill effects in pregnancy in animal models, and no adequate studies of its effects in human pregnancy have been conducted. Whether it can be passed by breastfeeding is unknown.[12] Adverse effectsMebendazole sometimes causes diarrhea, abdominal pain, and elevated liver enzymes. In rare cases, it has been associated with a dangerously low white blood cell count, low platelet count, and hair loss,[12][13] with a risk of agranulocytosis in rare cases Drug interactionsCarbamazepine and phenytoin lower serum levels of mebendazole. Cimetidine does not appreciably raise serum mebendazole (in contrast to the similar drug albendazole), consistent with its poor systemic absorption.[14][15]Stevens–Johnson syndrome and the more severe toxic epidermal necrolysis can occur when mebendazole is combined with high doses of metronidazole.[16]MechanismMebendazole works by selectively inhibiting the synthesis of microtubules via binding to colchicine binding site of β-tubulin, thereby blocking polymeration of tubulin dimers in intestinal cells of parasites.[17] Disruption of cytoplasmic microtubules leads to blocking the uptake of glucose and other nutrients, resulting in the gradual immobilization and eventual death of the helminths.[9] Poor absorption in digestive tract makes mebendazole an efficient drug for treating intestinal parasitic infections with limited adverse effects. However mebendazole has impact on mammalian cells mostly by inhibiting polymeration of tubulin dimers, thereby disrupting essential microtubule structures such as mitotic spindle.[18] Disassembly of mitotic spindle then leads to apoptosis mediated via dephosphorylation of Bcl-2 which allows pro-apoptotic protein Bax to dimerize and initiate programmed cell death.[19] Society and cultureAvailabilityMebendazole is available as a generic medication.[6] Mebendazole is distributed in international markets by Johnson and Johnson and a number of generic manufacturers.[20] CostIn the developing world the wholesale cost is between 0.004 and 0.04 USD per dose as of 2014.[7] In the United States a single dose was about 18 USD in 2015.[3] In 2016 the price increased to 440.00 USD per dose in the U.S. as Amedra Pharmaceuticals acquired the rights from Teva in 2013.[8] In 2010, Amedra also bought the U.S. marketing rights to the only other interchangeable anti-parasitic medication, albendazole, from GSK. The result of these acquisitions created a monopoly these medications and the price increased dramatically.[21] ResearchSeveral studies show mebendazole exhibits potent antitumor properties. MBZ significantly inhibited cancer cell growth, migration, and metastatic formation of adrenocortical carcinoma, both in vitro and in vivo.[22] Treatment of lung cancer cell lines with MBZ caused mitotic arrest, followed by apoptotic cell death with the feature of caspase activation and cytochrome c release.[23] MBZ induced a dose- and time-dependent apoptotic response in human lung cancer cell lines,[24] and apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells.[25] The anti-cancer effect of mebendazole comes from preclinical studies and case reports.[26] References1. ^{{cite book|last1=Ebadi|first1=Manuchair|title=Desk reference of clinical pharmacology|date=2008|publisher=CRC Press|location=Boca Raton|isbn=9781420047448|page=403|edition=2|url=https://books.google.com/books?id=ihxyHbnj3qYC&pg=PA403|deadurl=no|archiveurl=https://web.archive.org/web/20170908140525/https://books.google.com/books?id=ihxyHbnj3qYC&pg=PA403|archivedate=2017-09-08}} {{Anthelmintics}}{{portal bar|Pharmacy and pharmacology|Medicine}}2. ^{{cite web |url=http://www.evidence.nhs.uk/formulary/bnf/current/5-infections/55-anthelmintics/551-drugs-for-threadworms/mebendazole |title=MEBENDAZOLE |accessdate=2016-04-29 |deadurl=no |archiveurl=https://web.archive.org/web/20161023152521/http://www.evidence.nhs.uk/formulary/bnf/current/5-infections/55-anthelmintics/551-drugs-for-threadworms/mebendazole |archivedate=2016-10-23 }} 3. ^1 2 3 4 5 6 7 8 {{cite web|title=Mebendazole|url=https://www.drugs.com/monograph/mebendazole.html|publisher=The American Society of Health-System Pharmacists|accessdate=Aug 18, 2015|deadurl=no|archiveurl=https://web.archive.org/web/20150907003126/http://www.drugs.com/monograph/mebendazole.html|archivedate=2015-09-07}} 4. ^{{cite book|last1=Mehlhorn|first1=Heinz|title=Encyclopedic reference of parasitology. 107 tables|date=2001|publisher=Springer|location=Berlin [u.a.]|isbn=9783540668299|page=259|edition=2|url=https://books.google.com/books?id=OBZbR4vpg0YC&pg=PA259|deadurl=no|archiveurl=https://web.archive.org/web/20170908140525/https://books.google.com/books?id=OBZbR4vpg0YC&pg=PA259|archivedate=2017-09-08}} 5. ^{{cite web|title=WHO Model List of Essential Medicines (19th List)|url=http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|work=World Health Organization|accessdate=8 December 2016|date=April 2015|deadurl=no|archiveurl=https://web.archive.org/web/20161213052708/http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|archivedate=13 December 2016}} 6. ^1 {{cite book|last1=Hamilton|first1=Richard J.|title=Tarascon pocket pharmacopoeia|date=2012|publisher=Jones & Bartlett Learning|location=Burlington, Mass.|isbn=9781449624286|page=33|edition=13|url=https://books.google.com/books?id=BmKOS-b0s08C&pg=PA355|deadurl=no|archiveurl=https://web.archive.org/web/20170908140524/https://books.google.com/books?id=BmKOS-b0s08C&pg=PA355|archivedate=2017-09-08}} 7. ^1 {{cite web|title=Mebendazole|url=http://mshpriceguide.org/en/single-drug-information/?DMFId=493&searchYear=2014|website=International Drug Price Indicator Guide|accessdate=18 August 2015|deadurl=no|archiveurl=https://web.archive.org/web/20170305003745/http://mshpriceguide.org/en/single-drug-information/?DMFId=493&searchYear=2014|archivedate=5 March 2017}} 8. ^1 {{cite news|last1=Crow|first1=David|title=US drugmaker charges 200 times UK price for common worm pill|url=https://www.ft.com/content/f0080fe4-c3ad-11e6-9bca-2b93a6856354|accessdate=8 January 2017|work=www.ft.com|date=18 December 2016|subscription=yes|deadurl=no|archiveurl=https://web.archive.org/web/20170108061742/https://www.ft.com/content/f0080fe4-c3ad-11e6-9bca-2b93a6856354|archivedate=8 January 2017}} 9. ^1 2 Petri WA in Brunton LL, Chabner BA, Knollmann BC, Ed. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 12th ed., Chapter 42. McGraw-Hill, 2011 New York. 10. ^Martin AR in Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry, 8th edition, Doerge RF, ed. J.B. Lippincott, 1982, Chapter 4 11. ^{{cite web|title=Mebendazole|url=https://www.drugs.com/monograph/mebendazole.html|website=drugs.com|accessdate=25 January 2015|deadurl=no|archiveurl=https://web.archive.org/web/20150222112913/http://www.drugs.com/monograph/mebendazole.html|archivedate=22 February 2015}} 12. ^1 Finberg R, Fingeroth J in Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo, Ed. Harrison's Principles of Internal Medicine, 18th ed., McGraw-Hill, 2012, Chapter 217. 13. ^{{cite journal | vauthors = Andersohn F, Konzen C, Garbe E | title = Systematic review: agranulocytosis induced by nonchemotherapy drugs | journal = Ann. Intern. 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Pharmacol. | volume = 61 | issue = 5 | pages = 809–17 |date=April 2008 | pmid = 17581752 | doi = 10.1007/s00280-007-0538-0 }} 23. ^{{cite journal |vauthors=Sasaki J, Ramesh R, Chada S, Gomyo Y, Roth JA, Mukhopadhyay T | title = The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells | journal = Mol. Cancer Ther. | volume = 1 | issue = 13 | pages = 1201–9 |date=November 2002 | pmid = 12479701 | doi = }} 24. ^{{cite journal |vauthors=Mukhopadhyay T, Sasaki J, Ramesh R, Roth JA | title = Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo | journal = Clin. Cancer Res. | volume = 8 | issue = 9 | pages = 2963–9 |date=September 2002 | pmid = 12231542 | doi = }} 25. ^{{cite journal |vauthors=Doudican N, Rodriguez A, Osman I, Orlow SJ | title = Mebendazole induces apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells | journal = Mol. 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