简介：

硝唑尼特治疗慢性乙肝最新药品
    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）。
ALINIA TAB 500MG 60
(NITAZOXANIDE)
Generic Name: NITAZOXANIDE
Class: R
Manufacture: ROMARK PHARMACEUTICALS
Strength: 500MG
Size: 60
Unit: TAB
ALINIA TAB 500MG 30
(NITAZOXANIDE)
ALINIA ORAL SUSP 1CMG/5ML 60ML
(NITAZOXANIDE)
Romark实验室用硝唑尼特治疗12名慢性乙肝病人，4人HBeAg阳性，8人阴性，每天口服2次，每次500mg,治疗周期12个月。
4位HBeAg阳性病人，HBV DNA均大幅下降，3人HBeAg转阴，2人HBV DNA转阴，1人HBsAg转阴。
8位HBeAg阴性病人，7人HBV DNA转阴，2人HBsAg转阴。
还有两个个案：一个17岁的大三阳男性病人，治疗前，HBV DNA310000copies/ml,转氨酶25IU/ml，炎症3/18级，肝活检纤维化1/6，
用硝唑尼特治疗5个月，停了3个月，ALT升高，又用硝唑尼特每天500mg2年，HBsAg转阴，其它正常。另一个60岁大三阳男性病人，对拉米夫定，阿德福韦均无应答，
用硝唑尼特与阿德福韦联合治疗2年，HBsAg转阴，其它正常,第二项抗体出现。
从以上数据，可以看到各项转阴率都远超现有的药物。可惜的是样本量太少，无统计学意义。
硝唑尼特用于治疗丙肝也有非常好的疗效，已进入二期临床，初步实验数据已发表.
硝唑尼特(NTZ)是一种抗原虫药物，具有着广谱抗寄生虫和抗细菌感染作用。
Romark实验室正在研制第二代和具有缓释功能的thiazolides类药物。
实验显示，编号RM-4863
候选药物治疗丙肝的效果、耐受性比硝唑尼特更好，毒性更低。药效能稳定12－24小时。并去除了第一代硝唑尼特的广谱抗寄生虫和抗细菌感染功能。可能已进入临床（丙肝）。
从上面的介绍，第二代确实比第一代有很大的提高。治疗丙肝比第一代好，我想，乙肝也应该要好一点。硝唑尼特HBsAg转阴率在25％左右，第二代希望能达到40～50％
硝唑尼特更多资料
硝唑尼特(nitazoxanid，NTZ)是一种新的抗原虫药，由Romark实验室创制，首次报道于1976年，化学名称苯酚乙酸酯。
硝唑尼特可改善慢性丙肝的病毒学应答
美国胃肠病学会期刊日前发表一项研究，评估了硝唑尼特(nitrazoxa nide)联合聚乙二醇化干扰素α-2a与利巴韦林在慢性丙型肝炎(HCV)4型患者中的使用效果。研究显示，与只用聚乙二醇化干扰素α-2a加利巴韦林的标准治疗相比，在标准治疗外加用硝唑尼特可使患者持续病毒学应答率提高。
    这是一项随机对照研究，在埃及两个中心共招募了97名未经治疗的4型慢性丙型肝炎患者，评估硝唑尼特、聚乙二醇化干扰素α-2a和利巴韦林联合使用与只用聚乙二醇化干扰素α-2a加利巴韦林的安全性和疗效。
    研究主要终点为持续病毒学应答(SVR)，或治疗后24周血清HCV RNA<12IU/毫升。次要终点包括第4周(快速病毒学应答，或RVR)、第12周(完全早期病毒学应答，cEVR)以及治疗后(ETR)HCV RNA<12IU/毫升。
    结果发现，使用三联疗法与标准治疗相比，RVR(定义为联合治疗第4周时血清HCV RNA测不出)和SVR的患者百分比显著提高(分别为64%比38%，79%比50%)。接受硝唑尼特加聚乙二醇化干扰素α-2a的患者达到RVR和SVR的比例中等(分别为54%和61%)。
    各治疗组不良事件相似。在硝唑尼特治疗组，病毒学应答维持至治疗终末，无病毒学突破。值得注意的是，硝唑尼特的使用与复发率的降低相关。
    硝唑尼特是一类新的广谱抗病毒药，它是HCV在衍生复制子细胞系中的强力抑制剂，研究显示它不会诱导病毒突变产生耐药。
    近期一项Ⅱ期试验使用高低两种剂量的硝唑尼特控释片剂，显示其良好的药代动力学，使病毒载量显著降低，并有良好的耐受性和安全性。

硝唑尼特说明书

ALINIA
Alinia InformationAlinia is a medical product that is also well known as Nitazoxanide. This medication belongs to a wide class of drugs - antiprotozoals. Such products are widely prescribed in the therapy of diarrhea that has been triggered by a certain form of protozoa.
Alinia IndicationsAlinia is quite effective in the prophylaxis for diarrhea in the case of children and adults, if the symptom is caused by Giardia lamblia or other types of protozoa (including Cryptosporidium parvum). In other words, a therapy with this medicine is prescribed to patients who are diagnosed with travelers' diarrhea. However, a treatment trial with this medicine can prove effective in the therapy of some other medical conditions. It is important to refer to your personal health care provider if you have any further questions regarding this matter.
Alinia WarningsThe presence of other medical disorders (apart from traveler’s diarrhea) can prevent an individual from being prescribed a treatment trial with Alinia. For this reason, it is important to alert your personal health care provider if you are suffering from any immune system medical conditions (including HIV), kidney disorders or any liver medical conditions. While some patients who present these medical disorders will not be allowed to start using Alinia on a regular basis, others will be prescribed lower doses of this drug. However, their therapy with this antiprotozoal must be closely supervised by an authorized health care provider.
The oral form (suspension) of Alinia is known to contain about 1.48 grams of sucrose in a teaspoon of medicine (5 mL). This is why patients who are suffering from diabetes should lower their daily intake of sucrose during their therapy with this type of medicine.
Studies have shown that Nitazoxanide (Alinia) is a category B FDA pregnancy medicine. In other words, a treatment trial with this medical product should not harm a growing fetus in any way. However, it is best that each pregnant female who wants to start using this medicine on a regular basis should discuss the prospects of a potential therapy with Alinia with her personal health care provider. It has not yet been determined whether the ingredients of this medication are able to pass into the patient’s breast milk or not. In such conditions, we recommend all nursing mothers to stop breastfeeding their infants during their treatment trial with this medical product.
Alinia Intake GuidelinesYour personal health care provider is entitled to prescribe you the necessary precautions that you ought to take into consideration during your future therapy with Alinia. He or she will also tell you exactly how you should use each of your doses of this medical product.
All doses of Alinia should be accompanied with food. In this way, you will avoid experiencing the unpleasant symptoms of stomach disturbances. If you have been prescribed by your personal health care provider to use the suspension form of Alinia, we strongly advise you to make sure that you have well shaken the medicine before measuring your dose. Most physicians recommend their patients to measure their doses of Alinia with a special instrument (a dose measuring cup, dropper and / or spoon). If you do not own such devices, you should buy one from the nearest pharmacy. You may store your medicine at the average room temperature. Ask your pharmacist to tell you how you could discard the unused medicine.
Alinia DosageYour personal health care provider (your physician) will prescribe you the dose of Alinia that you should use on a regular basis, the one that will ensure that you will be granted the best effects from your treatment trial with this medicine. Periodically, your physician might want to alter your dose of this drug. It is important to follow each and every one of your doctor’s directions. Unauthorized alterations to your normal dosage of Alinia are not reccommended.
Alinia OverdoseAll patients who are suspected to be suffering from an overdose with Alinia ought to be granted immediate medical care. We have no information regarding the potential symptoms that this medical condition may trigger. For this reason, we advise you to ask your pharmacist, a nurse or a doctor for further information.
Alinia Missed DoseAny disruption in your regular Alinia therapy schedule will affect the beneficial results of your treatment trial with this drug. If you have missed using a dose of this medicine, we recommend you to skip the one that you have missed and to proceed with your regular treatment schedule. If you are unhappy with the therapy schedule that your physician has prescribed you, we advise you to contact your doctor and set up an appointment in which you will discuss you’re your physician which changes will suit you best.
Alinia Side EffectsIf an individual who is following a therapy with Alinia develops the severe symptoms of an allergic reaction (throat closure, breathing difficulties, swelling, hives, and so on), he or she should immediately stop their intake of this drug. A prolonged therapy with this medication may trigger the following less severe adverse reactions: headache, vomiting, diarrhea, nausea, abdominal pain, and so on.
Alinia Drug ReactionsStudies have shown that the way in which the ingredients of Alinia are metabolized by the patient’s organism can be affected by the intake of other medical products. Therefore, adjacent therapies that have not been authorized by the patient’s personal health care provider may easily lead to higher or lower levels of medicine in the patient’s blood