Chahine Elias B, Karaoui Lamis R, Mansour Hanine
Palm Beach Atlantic University, West Palm Beach, FL, USA.
Ann Pharmacother. 2014 Jan;48(1):107-15. doi: 10.1177/1060028013504087. Epub 2013 Nov 1.
To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosage, and administration of bedaquiline, a novel oral diarylquinoline antimycobacterial agent approved by the Food and Drug Administration for the treatment of adults with pulmonary multidrug-resistant tuberculosis (MDR-TB).
A search of PubMed (January 2004-May 2013) and International Pharmaceutical Abstracts (January 2004-May 2013) using the search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included proceedings of the Union World Conference on Lung Health.
Preclinical data as well as Phase 1 and 2 studies published in English were evaluated.
Bedaquiline possesses a unique mechanism of action that disrupts the activity of the mycobacterial adenosine triphosphate synthase. Clinical trials have been conducted evaluating the use of bedaquiline in combination with a background regimen for the treatment of adults with pulmonary MDR-TB. Bedaquiline has an excellent in vitro activity against Mycobacterium tuberculosis, including multidrug resistant M tuberculosis; however, its side effect profile limits its use against MDR-TB when no other effective regimen can be provided. Bedaquiline carries Black Box warnings for increased risk of unexplained mortality and QT prolongation. Bedaquiline is metabolized via the CYP3A4 isoenzyme and thus interacts with rifamycins and several antiretrovirals.
In an era of emerging resistance and given the suboptimal efficacy and toxicity of currently available regimens for MDR-TB, bedaquiline represents a great addition to the existing armamentarium of anti-TB agents particularly in areas of the world where the disease is endemic.
回顾贝达喹啉的化学、药理学、微生物学、药代动力学、药效学、临床疗效、安全性、剂量及用法。贝达喹啉是一种新型口服二芳基喹啉抗分枝杆菌药物，已获美国食品药品监督管理局批准用于治疗成人耐多药肺结核（MDR-TB）。
使用搜索词“贝达喹啉”“二芳基喹啉”“R207910”和“TMC207”对PubMed（2004年1月至2013年5月）和国际药学文摘（2004年1月至2013年5月）进行检索。补充来源包括世界肺部健康联盟会议的会议记录。
评估以英文发表的临床前数据以及1期和2期研究。
贝达喹啉具有独特的作用机制，可破坏分枝杆菌三磷酸腺苷合酶的活性。已开展临床试验评估贝达喹啉联合背景治疗方案用于治疗成人耐多药肺结核的效果。贝达喹啉对结核分枝杆菌具有优异的体外活性，包括耐多药结核分枝杆菌；然而，当无法提供其他有效治疗方案时，其副作用限制了它在耐多药结核病治疗中的应用。贝达喹啉有黑框警告，提示不明原因死亡率增加和QT间期延长风险。贝达喹啉通过CYP3A4同工酶代谢，因此与利福霉素类药物和几种抗逆转录病毒药物存在相互作用。
在耐药性不断出现的时代，鉴于目前可用的耐多药结核病治疗方案疗效欠佳且毒性较大，贝达喹啉是现有抗结核药物储备中的一大补充，尤其在该病流行的世界各地区。
