DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Infect Genet Evol. 2019 Oct;74:103937. doi: 10.1016/j.meegid.2019.103937. Epub 2019 Jun 24.
Rifampicin was discovered in 1965 and remains one of the most important drugs in tuberculosis treatment that is valued for its sterilizing activity and ability to shorten treatment. Antimicrobial activity of rifampicin was initially proved in vitro; subsequently numerous in vivo studies showed the bactericidal properties and dose-dependent effect of rifampicin. Rifampicin was first during the late 1960s to treat patients suffering from chronic drug-resistant pulmonary TB. Decades later, rifampicin continues to be studied with particular emphasis on whether higher doses could shorten the duration of treatment without increasing relapse or having adverse effects. Lesion-specific drug penetration and pharmacokinetics of rifampicin are improving our understanding of effective concentration while potentially refining drug regimen designs. Another prospective aspect of high-dose rifampicin is its potential use in treating discrepant mutation thereby eliminating the need for MDR treatment. To date, several clinical trials have shown the safety, efficacy, and tolerability of high-dose rifampicin. Currently, high-dose rifampicin has been used successfully in a routine clinical setting for the treatment of high-risk patients. However, the WHO and other relevant policy makers have not committed to implementing a controlled rollout thereof. This review describes the course that rifampicin has travelled to the present-day exploration of high-dose rifampicin treatment.
利福平于 1965 年被发现，至今仍是治疗结核病最重要的药物之一，其具有杀菌活性和缩短治疗时间的作用。利福平的抗菌活性最初在体外得到证实；随后，大量的体内研究表明利福平具有杀菌特性和剂量依赖性。利福平于 20 世纪 60 年代末首次用于治疗患有慢性耐药性肺结核的患者。几十年后，人们继续对利福平进行研究，特别关注高剂量是否可以在不增加复发或产生不良反应的情况下缩短治疗时间。利福平的病灶特异性药物渗透和药代动力学改善了我们对有效浓度的理解，同时有可能改进药物方案设计。高剂量利福平的另一个前瞻性方面是其在治疗异质性突变方面的潜在用途，从而无需进行耐多药治疗。迄今为止，多项临床试验表明了高剂量利福平的安全性、疗效和耐受性。目前，高剂量利福平已成功用于高危患者的常规临床治疗。然而，世界卫生组织和其他相关政策制定者尚未承诺实施控制推广。本综述描述了利福平从过去到现在探索高剂量利福平治疗的历程。
