Gras J
Drugs Today (Barc). 2013 Jun;49(6):353-61. doi: 10.1358/dot.2013.49.6.1970865.
After AIDS, tuberculosis (TB) is the leading killer worldwide due to a single infectious agent. Recently, drug-resistant strains of Mycobacterium tuberculosis elicited even more severe versions of TB. Bedaquiline inhibits mycobacterial ATP synthase. It shows potent and selective activity in vitro against M. tuberculosis, and in vivo against murine models of TB. Bedaquiline can be combined with antituberculosis and antiretroviral agents. The product displays good oral absorption, has a long terminal half-life and is metabolized mainly by cytochrome P450 3A4. In a phase II clinical trial in patients with multidrug-resistant TB, bedaquiline (combined with the standard five-drug, second-line TB regimen), showed a time to 50% culture negative conversion of 78 days, with 81.0% and 52.4% efficacy at weeks 24 and 104, respectively. Bedaquiline was generally safe and well tolerated. At the end of 2012, the U.S. Food and Drug Administration approved bedaquiline (Sirturo®) as part of a combination therapy to treat adults with multidrug-resistant TB.
继艾滋病之后，结核病是全球由单一传染源导致的主要杀手。近来，结核分枝杆菌的耐药菌株引发了更为严重的结核病。贝达喹啉可抑制分枝杆菌ATP合酶。它在体外对结核分枝杆菌显示出强效且有选择性的活性，在体内对结核病小鼠模型也有活性。贝达喹啉可与抗结核药和抗逆转录病毒药物联用。该产品口服吸收良好，终末半衰期长，主要通过细胞色素P450 3A4代谢。在一项针对耐多药结核病患者的II期临床试验中，贝达喹啉（与标准的五药二线抗结核方案联用）显示，50%培养转阴时间为78天，在第24周和第104周时的有效率分别为81.0%和52.4%。贝达喹啉总体上安全且耐受性良好。2012年底，美国食品药品监督管理局批准贝达喹啉（Sirturo®）作为联合治疗方案的一部分，用于治疗成人耐多药结核病。
