Nguyen T V A, Cao T B T, Akkerman O W, Tiberi S, Vu D H, Alffenaar J W C
a Department of Pharmacological, Medical and Agronomical Biotechnology , University of Science and Technology of Hanoi , Hanoi , Vietnam.
b Department of Clinical Pharmacy , Hanoi University of Pharmacy , Hanoi , Vietnam.
Expert Rev Clin Pharmacol. 2016 Aug;9(8):1025-37. doi: 10.1080/17512433.2016.1200462. Epub 2016 Jun 27.
Few innovative anti-microbial products have been brought to market in recent years to combat the global multidrug resistant-tuberculosis (MDR-TB) epidemic. Bedaquiline, a novel oral diarylquinoline, was approved by the US FDA as a part of combination therapy in adults with pulmonary MDR-TB based on phase II trials.
Pubmed searches were conducted using search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included World Health Organization, Clinicaltrial.gov, US Food and Drug Administration. Bedaquiline is an ATP synthase inhibitor specific for M. tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4 and it's drug exposure can be influenced by inducers and inhibitors of this enzyme. Phase II studies showed promising results on efficacy of bedaquiline when being used in combination with a background regimen for MDR-TB. Main safety concerns include QTc prolongation and hepatotoxicity. Phase III trials are ongoing to confirm efficacy findings from phase II studies and provide additional evidence of safety and efficacy. Expert commentary: Critical data for long-term efficacy and safety are incomplete and scarce, supporting the cautious use of bedaquiline.
近年来，几乎没有创新的抗菌产品投放市场以应对全球耐多药结核病（MDR-TB）疫情。贝达喹啉是一种新型口服二芳基喹啉，基于II期试验，被美国食品药品监督管理局（FDA）批准作为成人肺部MDR-TB联合治疗的一部分。
使用搜索词“贝达喹啉”“二芳基喹啉”“R207910”和“TMC207”在PubMed上进行了检索。补充来源包括世界卫生组织、Clinicaltrial.gov、美国食品药品监督管理局。贝达喹啉是一种对结核分枝杆菌和一些非结核分枝杆菌具有特异性的ATP合酶抑制剂。它由CYP3A4代谢，其药物暴露可受该酶的诱导剂和抑制剂影响。II期研究显示，贝达喹啉与MDR-TB背景治疗方案联合使用时，在疗效方面有令人鼓舞的结果。主要的安全问题包括QTc延长和肝毒性。III期试验正在进行，以确认II期研究的疗效结果，并提供更多安全性和有效性证据。专家评论：长期疗效和安全性的关键数据不完整且稀缺，这支持谨慎使用贝达喹啉。
