Drugs in Development for Tuberculosis
Drugs in Development for Tuberculosis
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DOI：
10.2165/11538170-000000000-00000
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发表时间：
2010-01-01
期刊：
影响因子：
11.5
通讯作者：
Ginsberg, Ann M.
中科院分区：
文献类型：
--
作者：
Ginsberg, Ann M.
过去 10 年来，结核病 (TB) 药物研发工作重新兴起，以满足迫切的医疗需求，但仍然存在巨大的挑战。这些迫切的需求主要是由当前漫长而艰巨的多药治疗方案驱动的，这些治疗方案存在重大的安全性、耐受性和依从性问题，多药耐药和广泛耐药结核病的发病率不断上升且令人不安，大约 20 亿人已经潜伏感染结核病病原体结核分枝杆菌，以及全球结核病与艾滋病毒共流行 结核病药物开发的利益相关者正在努力推动并简化新型多药治疗方案的开发和注册，该治疗方案由多种具有新颖作用机制的新化学实体组成，不会对当前一线和二线结核病药物产生交叉耐药性。理想情况下，这些新方案最终将提供一种短期、简单的治疗方法，适用于基本上所有结核病患者，无论对当前抗结核药物敏感还是耐药，无论是 HIV 阳性还是阴性，也无论患者年龄本文回顾了那些试图开发这些新疗法的人所面临的挑战以及目前正在进行结核病临床测试的关键药物，后者分为三类进行讨论：(i) 新药（TMC207、SQ109 sudoterb [LL3858]）、00 目前正在重新评估以优化其疗效的一线结核病药物（利福平、利福喷汀），以及（in）目前许可用于其他适应症和“下一代”的药物同一化学类别的化合物被重新用于结核病治疗（加替沙星和莫西沙星、利奈唑胺、PNU100480 和 AZD5847、甲硝唑、OPC-67683 和 PA 824）
Tuberculosis (TB) drug research and development efforts have resurged in the past 10 years to meet urgent medical needs, but enormous challenges remain These urgent needs are largely driven by the current long and arduous multidrug regimens, which have significant safety, tolerability and compliance issues, rising and disturbing rates of multidrug- and extensively drug-resistant TB, the existence of approximately 2 billion individuals already latently infected with Mycobacterium tuberculosis, the causative pathogen of TB, and a global TB-HIV co-epidemic Stakeholders in TB drug development are moving to enable and streamline development and registration of novel, multidrug treatment regimens, comprised of multiple new chemical entities with novel mechanisms of action that do not demonstrate cross-resistance to current first- and second-line TB drugs Ideally, these new regimens will ultimately provide a short, simple treatment suitable for essentially all TB patients, whether sensitive or resistant to the current anti-TB agents, whether HIV-positive or -negative, and irrespective of patient ageThis article reviews the challenges faced by those trying to develop these novel regimens and the key agents currently in clinical testing for TB, the latter are organized for discussion into three categories (i) novel drugs (TMC207, SQ109 sudoterb [LL3858]), 00 present first-line TB drugs being re evaluated to optimize their efficacy (rifampicin, rifapentine), and (in) currently licensed drugs for other indications and 'next-generation' compounds of the same chemical class being repurposed for TB (gatifloxacin and moxifloxacin, linezolid, PNU100480 and AZD5847, metronidazole, OPC-67683 and PA 824)