给战友点希望－－硝唑尼特治疗慢肝

乙者

有没有实用一点的消息，等的花儿也谢了

闹心啊

此药最近很难有什么实质性的好消息，因为没有进行乙肝的临床试验。ROMARK实验室的精力都集中到丙肝上了。丙肝的二期试验已有多个，有的已结束，有的正在进行，包括控释型的硝唑尼特。
乙肝的临床试验估计还得等等。我感觉乙肝的临床试验不会再是硝唑尼特，而是第二代硝唑尼特。ROMARK实验室正在筛选第二代硝唑尼特，看看哪一个效果好。据说RM4863效果比较不错。见图片上的药物的结构式对比。
硝唑尼特的希望还是挺大的，效果及有可能超过国内在研的治疗性疫苗。
有兴趣的战友，可以买来原料药尝试一下。估计副作用不大，因为已上市好几年了，儿童都可以吃。[attachimg]129416[/attachimg]

[ 本帖最后由 闹心啊 于 2009-11-28 16:33 编辑 ]

乙者

到哪买呀？买到了又怎么用？

齐欢畅2

齐欢畅2

妄自菲薄

能使HBsAg转阴这么牛啊？厉害！

齐欢畅2

齐欢畅2

Summary
Future Microbiology
October 2008, Vol. 3, No. 5, Pages 539-545 , DOI 10.2217/17460913.3.5.539
(doi:10.2217/17460913.3.5.539)



Review
Thiazolides: a new class of drugs for the treatment of chronic hepatitis B and C
Jean-François Rossignol‌ & Emmet B Keeffe‌†
†Author for correspondence




Nitazoxanide, the first thiazolide, was originally developed for the treatment of Cryptosporidium parvum. The antiviral activity of nitazoxanide was discovered by serendipity in patients with AIDS who were treated for cryptosporidial diarrhea and had HBV or HCV co-infection. In preliminary open-label studies of patients with chronic hepatitis B, nitazoxanide suppressed serum HBV DNA and led to loss or seroconversion of hepatitis B e antigen in the majority of patients, as well as hepatitis B surface antigen in approximately a quarter of patients. In Phase II studies of patients with chronic hepatitis C genotype 4, nitazoxanide combined with peginterferon alfa-2a, with or without ribavirin, increased the sustained virologic response rate to 79–80 versus 50% with peginterferon plus ribavirin standard of care. Randomized, controlled studies of naive and nonresponder patients with chronic hepatitis C genotype 1 and patients with chronic hepatitis B are underway, and new second generation thiazolides are being developed.

齐欢畅2

Nitazoxanide, tizoxanide and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication




References and further reading may be available for this article. To view references and further reading you must purchase this article.


Brent E. Korbaa, , , Abigail B. Monteroa, Kristine Farrara, Karen Gayea, Sampa Mukerjeea, Marc S. Ayersb and Jean-François Rossignolb, c

aDepartment of Microbiology and Immunology, Georgetown University Medical Center, 3900 Reservoir Rd. Washington, DC20007 USA

bThe Romark Institute for Medical Research, 3000 Bayport Drive, Tampa, FL 33607 USA

cDivision of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA 94305, USA


Received 13 February 2007;  accepted 10 August 2007.  Available online 4 September 2007.

Abstract
Nitazoxanide (NTZ), a thiazolide anti-infective, is active against anaerobic bacteria, protozoa, and a range of viruses in cell culture models, and is currently in phase II clinical development for treating chronic hepatitis C. In this report, we characterize the activities of NTZ and its active metabolite, tizoxanide (TIZ), along with other thiazolides against hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in standard antiviral assays. NTZ and TIZ exhibited potent inhibition of both HBV and HCV replication. NTZ was equally effective at inhibiting replication of lamivudine (LMV) and adefovir dipovoxil (ADV)-resistant HBV mutants and against 2′-C-methyl cytidine (2′CmeC) and telaprevir (VX-950)-resistant HCV mutants. NTZ displayed synergistic interactions with LMV or ADV against HBV, and with recombinant interferon alpha-2b (IFN) or 2′CmeC against HCV. Pre-treatment of HCV replicon-containing cells with NTZ potentiated the effect of subsequent treatment with NTZ plus IFN, but not NTZ plus 2′CmeC. NTZ induced reductions in several HBV proteins (HBsAg, HBeAg, HBcAg) produced by 2.2.15 cells, but did not affect HBV RNA transcription. NTZ, TIZ, and other thiazolides are promising new antiviral agents that may enhance current or future anti-hepatitis therapies.

Keywords: Hepatitis B virus; Hepatitis C virus; Nitazoxanide; Thiazolides; Antiviral therapy

齐欢畅2

硝唑尼特（Nitazoxanide，Alinia)治疗丙肝
2009-10-26 10:23:30  作者：  来源：互联网  浏览次数：37  文字大小：【大】【中】【小】
简介：硝唑尼特治疗慢性乙肝最新动态 硝唑尼特（Nitazoxanide，Alinia®, Romark Laboratories, L.C., Tampa, Fl, USA)是第一个thiazolide类药物，2002年在美国获得批准，用于治疗免疫功能健全的成人和儿童的 ...
关键字：硝唑尼特 Nitazoxanide Alinia
硝唑尼特治疗慢性乙肝最新动态  

    硝唑尼特（Nitazoxanide，Alinia®, Romark Laboratories, L.C., Tampa, Fl, USA)是第一个thiazolide类药物，2002年在美国获得批准，用于治疗免疫功能健全的成人和儿童的小球隐孢子虫和蓝氏贾第虫感染。而现在大量的临床前及临床试验表明硝唑尼特对于乙肝病毒和丙肝病毒感染有活性。
抗病毒作用机制
    硝唑尼特抗原虫和厌氧菌的作用机制是直接抑制丙酮酸铁氧还蛋白氧化还原酶反应。但其抗病毒作用机制与此不同。其作用机制可能是激活一种蛋白激酶，这种蛋白激酶可以被双链RNA激活，而这种蛋白激酶也是干扰素诱导的抗病毒反应的中介物质。这种蛋白激酶称为PKR，其激活导致底物真核启动因子2α(eIF2a)的磷酸化。硝唑尼特代表了一类新作用机制的抗病毒药，由于其针对宿主的抗病毒机制，因此发生病毒耐药的门槛要显著高于直接针对病毒的药物。
抗乙肝和丙肝病毒体外活性
    最初是在应用硝唑尼特治疗艾滋病人原虫感染时偶然发现其具有抗肝病毒活性，其后应用标准的体外抗病毒检测方法证实了硝唑尼特及其代谢物替唑尼特的抗病毒活性。硝唑尼特和替唑尼特都是潜在的乙肝病毒抑制剂，与其它抗病毒药物如拉米夫定、阿德福韦联用具有协同效应，硝唑尼特和替唑尼特同样对耐受拉米夫定、阿德福韦的乙肝病毒变异体有效。此外，在以a-和1b基因型启动复制子的细胞和2a基因型细胞培养模型中，硝唑尼特和替唑尼特也是潜在的丙肝病毒抑制剂，与干扰素联用具有协同效应。以硝唑尼特预先处理丙肝病毒复制模型三天，使病毒对之后的干扰素治疗更敏感，这为正在进行的联合治疗之前采用硝唑尼特导入期的临床研究提供了依据。
治疗慢性乙肝
    单独使用硝唑尼特治疗慢性乙肝（疗程为一年）的疗效已得到初步证明，每天两次，每次500mg硝唑尼特的给药方案使4名HBeAg阳性患者血清乙肝病毒DNA水平全部出现下降，4名患者中2名患者乙肝病毒DNA含量降低到检测水平以下，3名患者HBeAg转阴，1名患者HBsAg转阴。8名HBeAg阴性患者中7名患者乙肝病毒DNA降低到检测水平以下，2名患者HBsAg转阴。另外，硝唑尼特单独治疗组有1例，硝唑尼特加阿德福韦联合治疗组也有1例患者在治疗后，获得了乙肝病毒DNA低于检测水平，HBeAg和HBsAg抗原转阴的效果。这些初步研究结果显示硝唑尼特治疗HBsAg转阴率要高于目前已批准的其他任何乙肝治疗药物。与干扰素相似的作用机制提示，硝唑尼特单独使用或与核苷(酸)类似物联用都可能使HBsAg阴转率提高（治疗终极终点）。一项正式的Ⅱ期试验计划将于2009年启动（但检索尚未发现硝唑尼特治疗乙肝的临床试验注册信息）。