Alfarisi Omamah, Alghamdi Wael A, Al-Shaer Mohammad H, Dooley Kelly E, Peloquin Charles A
a Department of Medicine , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
b Department of Pharmacotherapy and Translational Research , University of Florida, College of Pharmacy , Gainesville , FL , USA.
Expert Rev Clin Pharmacol. 2017 Oct;10(10):1027-1036. doi: 10.1080/17512433.2017.1366311. Epub 2017 Aug 18.
One-third of the world's population is infected with Mycobacterium tuberculosis (M.tb.). Latent tuberculosis infection (LTBI) can progress to tuberculosis disease, the leading cause of death by infection. Rifamycin antibiotics, like rifampin and rifapentine, have unique sterilizing activity against M.tb. What are the advantages of each for LTBI or tuberculosis treatment? Areas covered: We review studies assessing the pharmacokinetics (PK), pharmacodynamics (PD), drug interaction risk, safety, and efficacy of rifampin and rifapentine and provide basis for comparing them. Expert commentary: Rifampin has shorter half-life, higher MIC against M.tb, lower protein binding, and better distribution into cavitary contents than rifapentine. Drug interactions for the two drugs maybe similar in magnitude. For LTBI, rifapentine is effective as convenient, once-weekly, 12-week course of treatment. Rifampin is also effective for LTBI, but must be given daily for four months, therefore, drug interactions are more problematic. For drug-sensitive tuberculosis disease, rifampin remains the standard of care. Safety profile of rifampin is better-described; adverse events differ somewhat for the two drugs. The registered once-weekly rifapentine regimen is inadequate, but higher doses of either drugs may shorten the treatment duration required for effective management of TB. Results of clinical trials evaluating high-dose rifamycin regimens are eagerly awaited.
世界三分之一的人口感染了结核分枝杆菌(M.tb.)。潜伏性结核感染(LTBI)可能会发展为结核病,而结核病是感染导致死亡的主要原因。利福霉素类抗生素,如利福平和利福喷汀,对结核分枝杆菌具有独特的杀菌活性。它们各自在LTBI或结核病治疗中有哪些优势呢?涵盖领域:我们回顾了评估利福平和利福喷汀的药代动力学(PK)、药效学(PD)、药物相互作用风险、安全性和疗效的研究,并为比较它们提供依据。专家评论:与利福喷汀相比,利福平半衰期较短,对结核分枝杆菌的最低抑菌浓度(MIC)较高,蛋白结合率较低,在空洞内容物中的分布更好。两种药物的药物相互作用程度可能相似。对于LTBI,利福喷汀作为一种方便的每周一次、为期12周的治疗方案是有效的。利福平对LTBI也有效,但必须每日给药四个月,因此,药物相互作用问题更大。对于药物敏感的结核病,利福平仍然是治疗的标准药物。利福平的安全性特征描述得更完善;两种药物的不良事件略有不同。已注册的利福喷汀每周一次治疗方案并不充分,但两种药物的更高剂量可能会缩短有效治疗结核病所需的疗程。评估高剂量利福霉素治疗方案的临床试验结果备受期待。