伊维菌素

抗寄生虫药物

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[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]

伊维菌素
临床资料
怀孕分级
  • C
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
  • Ivermectin(22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b
CAS号70288-86-7  checkY
71827-03-7
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB配体ID
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
ECHA InfoCard100.067.738 编辑维基数据链接
化学信息
化学式C48H74O14
摩尔质量875.11 g·mol−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

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默克药厂默克治疗研究所的威廉·坎贝尔阿维菌素提纯出来[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大村,理由是“这种衍生物从根本上降低了河盲症淋巴丝虫病(“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

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

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 (2021-06)。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英语Brazilian Health Regulatory Agency、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

参考资料

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