伊维菌素
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临床资料 | |
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怀孕分级 |
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给药途径 | 口服 |
ATC码 | |
药物动力学数据 | |
血浆蛋白结合率 | 93% |
药物代谢 | 肝脏; CYP450 |
生物半衰期 | 18小时 |
排泄途径 | 粪便; 尿液<1% |
识别信息 | |
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CAS号 | 70288-86-7 ![]() 71827-03-7 |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEMBL | |
PDB配体ID | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.067.738 |
化学信息 | |
化学式 | C48H74O14 |
摩尔质量 | 875.11 g·mol−1 |
伊维菌素(英语:ivermectin)也称为爱获灭,是一种阿维菌素家族[1]有效抗多种寄生虫的治疗药物[2],其适用于治疗头虱[1]、疥螨引起的疥疮[3],蟠尾丝虫症(河盲症)[4],线虫感染[5],班氏丝虫感染导致的象皮病等[6]。伊维菌素可以涂抹于皮肤或是口服,但应避免接触眼睛[1]
常见的副作用包含眼睛红痒,皮肤干燥与灼烧感[1]。目前尚不清楚在孕期中使用是否安全,但是在哺乳期使用似乎尚可[7]。其作用机制是使增加无脊椎动物的细胞膜可透性,导致它们死亡。
伊维菌素发现于1975年,并在1981年列为药物[6][8]。 它是世界卫生组织基本药物标准清单中的一部分,是基层健康卫生系统中非常重要的药物[9]。一套治疗流程需要的药物售价约为0.12美金[10],在美国约要价25到50美金[5],在其他的动物身上,伊维菌素用于治疗与预防犬心丝虫等疾病[2]。
历史
[编辑]伊维菌素这种高效低毒的药品由日本北里大学有机化学家大村智和默克药厂默克治疗研究所的威廉·坎贝尔从阿维菌素提纯出来[11],并于1981年被引入治疗[12]。2015年度的诺贝尔生理学或医学奖的一半联合授予坎贝尔和大村,理由是“这种衍生物从根本上降低了河盲症和淋巴丝虫病(“象皮病”)的发病率,以及有效对抗快速增加中的其他寄生虫疾病“[13]。
在其他动物的用途
[编辑]伊维菌素对绵羊疥癣有高度治愈力。同时,它也能对抗羊痂恙虫、绵羊虱蝇、羊狂蝇的幼虫及胃肠中大部分的线虫和肺寄生虫,且能控制绿头苍蝇的排泄物引起的蝇蛆病。使用在绵羊疥癣上时,最常用的剂型为长效型伊维菌素控制释放胶囊。
研究
[编辑]伊维菌素在体外对包括SARS-CoV-2在内的若干正单链RNA病毒有抗病毒作用。[14]后续研究发现本药在猴肾细胞对SARS-CoV-2的半抑制浓度为2.2–2.8μM。[15][16]伊维菌素在人体内达到抗病毒作用所需剂量远高于人用最高批准剂量、亦超过可安全实现剂量。[17][18]本药通过抑制输入蛋白α/β1的核运输达到抗病毒作用,在上述剂量下对宿主有毒。[19]因此现在缺乏展开本药COVID-19的临床检验的理由。[20]
多人因服用马用伊维菌素浓缩剂住院;过度用药亦已导致死亡病例;病人可能因本药与其他药物相互作用死亡。[21]截至2021年6月[update]。为解决原有小规模、低质量研究的不确定之处,美国和英国展开了大规模临床研究。[22][23]
众多学者对本药运用于COVID-19的研究有重大方法缺陷,证据水平因此很低。[20][24][25]众多组织因此公开表示本药对于治疗COVID-19有效的证据薄弱。2021年2月,本药的研发厂商默克发表声明表示目前没有本药对COVID-19有效的适当证据、以此目的使用本药亦相当危险。[26][27]美国国立卫生研究院COVID-19治疗指南表示本药证据极其有限,无法做出任何建议。[28]英国全国COVID-19治疗咨询委员会认定本药用于COVID-19治疗的证据和可行性不足以进行下一步调查.[29]
美国食品药品监督管理局(FDA)未批准本药在美国治疗任何病毒疾病、在欧洲亦未获准用于治疗COVID-19。[28][30] 在审核本药相关证据后,欧洲药品管理局(EMA)表示目前数据不支持在良好设计的临床试验外使用本药。[30]2021年3月,FDA及EMA皆发布指南表示不应使用本药治疗COVID-19。[21][30]世界卫生组织亦表示本药除临床试验外不应用于治疗COVID-19。[31]巴西国家卫生监督局、巴西传染病学会、巴西胸腔学会发布声明反对使用本药预防或治疗早期COVID-19。[32][33][34]
参见
[编辑]参考资料
[编辑]- ^ 1.0 1.1 1.2 1.3 Ivermectin. The American Society of Health-System Pharmacists. [Jan 2016]. (原始内容存档于2016-01-03).
- ^ 2.0 2.1 Saunders Handbook of Veterinary Drugs: Small and Large Animal 4. Elsevier Health Sciences. 2015: 420 [2016-01-24]. ISBN 9780323244862. (原始内容存档于2016-01-31).
- ^ Panahi, Y; Poursaleh, Z; Goldust, M. The efficacy of topical and oral ivermectin in the treatment of human scabies.. Annals of parasitology. 2015, 61 (1): 11–6. PMID 25911032.
- ^ Sneader, Walter. Drug Discovery a History.. Chichester: John Wiley & Sons. 2005: 333 [2016-01-24]. ISBN 9780470015520. (原始内容存档于2016-01-31).
- ^ 5.0 5.1 Hamilton, Richard J. Tarascon pocket pharmacopoeia : 2014 deluxe lab-pocket edition 15th edition. Sudbury: Jones & Bartlett Learning. 2014: 422 [2016-01-24]. ISBN 9781284053999. (原始内容存档于2016-01-31).
- ^ 6.0 6.1 Mehlhorn, Heinz. Encyclopedia of parasitology 3rd ed. Berlin: Springer. 2008: 646 [2016-01-24]. ISBN 9783540489948. (原始内容存档于2016-01-31).
- ^ Ivermectin Levels and Effects while Breastfeeding. [2016-01-16]. (原始内容存档于2016-01-01).
- ^ Vercruysse, edited by J.; Rew, R.S. Macrocyclic lactones in antiparasitic therapy. Oxon, UK: CABI Pub. 2002: Preface [2016-01-24]. ISBN 9780851998404. (原始内容存档于2016-01-31).
- ^ WHO Model List of Essential Medicines (PDF). World Health Organization. October 2013 [2014-04-22]. (原始内容存档 (PDF)于2014-04-23).
- ^ Ivermectin. International Drug Price Indicator Guide. [2016-01-16].[永久失效链接]
- ^ Fisher MH, Mrozik H. The chemistry and pharmacology of avermectins. Annu. Rev. Pharmacol. Toxicol. 1992, 32: 537–53. PMID 1605577. doi:10.1146/annurev.pa.32.040192.002541.
- ^ W. C. CAMPBELL; R. W. BURG, , M. H. FISHER, and , R. A. DYBAS. The Discovery of Ivermectin and Other Avermectins. American Chemical Society: 5–20. 1984-06-26 [2015-10-09]. ISBN 9780841210837. (原始内容存档于2019-06-01).
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被忽略 (帮助) - ^ The Nobel Prize in Physiology or Medicine 2015. Nobel Foundation. [2020-05-06]. (原始内容存档于2021-02-09).
- ^ Heidary F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. The Journal of Antibiotics. September 2020, 73 (9): 593–602. PMC 7290143
. PMID 32533071. doi:10.1038/s41429-020-0336-z.
- ^ Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research. April 2020, 178: 104787. PMC 7129059
. PMID 32251768. doi:10.1016/j.antiviral.2020.104787.
- ^ Şimşek Yavuz S, Ünal S. Antiviral treatment of COVID-19. Turkish Journal of Medical Sciences. April 2020, 50 (SI-1): 611–619. PMC 7195979
. PMID 32293834. doi:10.3906/sag-2004-145
.
- ^ Bray M, Rayner C, Noël F, Jans D, Wagstaff K. Ivermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses. Antiviral Research. June 2020, 178: 104805. PMC 7172803
. PMID 32330482. doi:10.1016/j.antiviral.2020.104805.
- ^ López-Medina E, López P, Hurtado IC, Dávalos DM, Ramirez O, Martínez E, et al. Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19. JAMA. 2021-03-04, 325 (14): 1426–1435 [2021-07-11]. ISSN 0098-7484. PMC 7934083
. PMID 33662102. doi:10.1001/jama.2021.3071. (原始内容存档于2021-07-31).
- ^ Yang SN, Atkinson SC, Wang C, Lee A, Bogoyevitch MA, Borg NA, Jans DA. The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer (PDF). Antiviral Research. May 2020, 177: 104760 [2021-07-11]. PMID 32135219. doi:10.1016/j.antiviral.2020.104760. (原始内容存档 (PDF)于2020-07-13).
- ^ 20.0 20.1 Garegnani LI, Madrid E, Meza N. Misleading clinical evidence and systematic reviews on ivermectin for COVID-19. BMJ Evidence-Based Medicine. 2021-04-22 [2021-07-11]. ISSN 2515-446X. PMID 33888547. doi:10.1136/bmjebm-2021-111678
. (原始内容存档于2021-05-28).
- ^ 21.0 21.1 Why You Should Not Use Ivermectin to Treat or Prevent COVID-19. U.S. Food and Drug Administration (FDA). 5 March 2021 [5 March 2021]. (原始内容存档于2021-08-06).
- ^ Schraer, Rachel. Covid: Ivermectin to be studied as possible treatment in UK. BBC News. 23 June 2021 [23 June 2021]. (原始内容存档于2021-07-20).
- ^ COVID-19 Therapeutics Prioritized for Testing in Clinical Trials. National Institutes of Health. [27 June 2021]. (原始内容存档于2021-08-05).
- ^ Bartoszko JJ, Siemieniuk RA, Kum E, Qasim A, Zeraatkar D, et al. Prophylaxis against covid-19: living systematic review and network meta-analysis. BMJ (Systematic review). April 2021, 373: n949. PMC 8073806
. PMID 33903131. doi:10.1136/bmj.n949.
- ^ Roman YM, Burela PA, Pasupuleti V, Piscoya A, Vidal JE, Hernandez AV. Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials. Clinical Infectious Diseases. 28 June 2021 [2021-07-11]. ISSN 1058-4838. PMID 34181716. doi:10.1093/cid/ciab591. (原始内容存档于2021-08-06).
- ^ Gorski DH. Ivermectin is the new hydroxychloroquine. Science-Based Medicine. 15 April 2021 [2021-07-11]. (原始内容存档于2021-07-12).
- ^ Merck Statement on Ivermectin use During the COVID-19 Pandemic. Merck. 4 February 2021 [2021-07-11]. (原始内容存档于2021-08-03).
- ^ 28.0 28.1 The COVID-19 Treatment Guidelines Panel's Statement on the Use of Ivermectin for the Treatment of COVID-19. National Institutes of Health. 14 January 2020 [2021-07-11]. (原始内容存档于2021-02-08).
- ^ Wadvalla BA. Covid-19: Ivermectin's politicisation is a warning sign for doctors turning to orphan treatments. BMJ. April 2021, 373: n747. PMID 33795225. S2CID 232484313. doi:10.1136/bmj.n747
.
- ^ 30.0 30.1 30.2 EMA advises against use of ivermectin for the prevention or treatment of COVID-19 outside randomised clinical trials (新闻稿). European Medicines Agency. 22 March 2021 [2021-07-11]. (原始内容存档于2021-08-04).
- ^ WHO advises that ivermectin only be used to treat COVID-19 within clinical trials. World Health Organisation. 31 March 2021 [2021-07-11]. (原始内容存档于2021-08-05).
- ^ Quintanilha, Dayana de Oliveira. Anvisa se manifesta contra o uso da ivermectina na Covid-19 [Anvisa speaks out against the use of ivermectin in Covid-19]
. PEBMED. 2020-07-13 [2021-07-11]. (原始内容存档于2021-07-12) (葡萄牙语).
- ^ Atualizações e Recomendações sobre a Covid-19 [Updates and recommendations on Covid-19] (PDF). Sociedade Brasileira de Infectologia. 2020-12-09 [2021-07-11]. (原始内容存档 (PDF)于2021-03-22) (葡萄牙语).
- ^ Posicionamento da Sociedade Brasileira de Pneumologia e Tisiologia Sobre o Colapso em Manaus e Tratamento Preventivo e Precoce da Covid-19 [Brazilian Thoracic Society Position Statement on the Collapse in Manaus and the Preventive and Early Treatment of Covid-19]. Sociedade Brasileira de Pneumologia e Tisiologia. 2021-01-17 [2021-01-18]. (原始内容存档于2021-07-12) (葡萄牙语).
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