Patel Naresh, Jagannath K, Vora Agam, Patel Mukesh, Patel Anand
Professor, Department of Chest Disease and Tuberculosis, CU Shah Medical College, Surendranagar, Gujarat.
Director, Chennai Thoracic Research Institute, Chennai, Tamil Nadu.
J Assoc Physicians India. 2017 Sep;65(9):48-54.
The overall goals for treatment of Tuberculosis (TB) are to cure individual patient and to minimize the transmission of Mycobacterium tuberculosis. At the time of study conduction, the standard treatment for newly diagnosed tuberculosis patients consisted of an intensive phase for two months with four drugs (HRZE), followed by continuation phase for four months with two drugs (HR). Rifampicin, which is very effective against Mycobacterium tuberculosis, in both the phases of treatment, has certain concerns, which includes, decreased bioavailability with chronic use and hepatotoxicity. To overcome these concerns a new boosted formulation of Rifampicin (Risorine) with bio-enhancer Piperine was developed. Piperine has been found to increase bioavailability of several drugs including Amoxicillin, Cefotaxime, Theophylline and Propranolol. Risorine is a fixed dose combination that contains Rifampicin 200 mg + Isoniazid 300 mg + Piperine 10 mg.
The aim of the present study was to validate the therapeutic efficacy and tolerability of Risorine formulation containing regimen with a conventional regimen in the management of patients with newly diagnosed pulmonary tuberculosis.
Total 216 patients with sputum positive and treatment naïve pulmonary tuberculosis were enrolled in the study after fulfillment of inclusion / exclusion criteria. These patients were randomized to receive either a conventional anti-TB therapy (n = 117) or a similar regimen containing Risorine (n = 99) for 6 months. During the study period, symptomatic improvement, sputum conversion and radiological improvement were monitored at regular intervals.
Of the 216 enrolled patients, 75% in the Risorine group and 79% in the control group completed the study. At 4 weeks the sputum conversion rate was significantly superior in Risorine group (93%) than the control group (84%), which was consistence throughout the study. Cure rate at the end of 24 weeks, was higher in Risorine group (92%) than in the control group (82%). Elevation of liver enzymes were observed in 3 patients in the Risorine group and in 9 patients in control group.
Risorine, a novel formulation of low dose Rifampicin (200 mg), a bio enhancer Piperine (10 mg) and standard dose Isoniazid (300 mg) when given along with Ethambutol and Pyrazinamide was comparable in efficacy with standard WHO therapy using conventional formulation. Risorine provides more Rifampicin in blood compare to GI tract as well as maintaining higher blood levels on chronic therapy compared to conventional Rifampicin with better safety profile. Risorine gives higher sputum conversion rate during the Intensive Phase which is maintained till the end of study. Further a trend was also noticed towards better tolerability with newer formulation, Risorine. H = Isoniazid, R = Rifampicin, Z = Pyrazinamide and E = Ethambutol.
结核病（TB）治疗的总体目标是治愈个体患者并尽量减少结核分枝杆菌的传播。在开展本研究时，新诊断结核病患者的标准治疗方案包括为期两个月的强化期，使用四种药物（HRZE），随后是为期四个月的持续期，使用两种药物（HR）。利福平在治疗的两个阶段对结核分枝杆菌都非常有效，但存在一些问题，包括长期使用生物利用度降低和肝毒性。为克服这些问题，开发了一种新的利福平增强制剂（Risorine），其含有生物增强剂胡椒碱。已发现胡椒碱可提高包括阿莫西林、头孢噻肟、茶碱和普萘洛尔在内的多种药物的生物利用度。Risorine是一种固定剂量组合，含有利福平200毫克+异烟肼300毫克+胡椒碱10毫克。
本研究的目的是在新诊断的肺结核患者管理中，验证含Risorine制剂方案与传统方案的治疗效果和耐受性。
在满足纳入/排除标准后，共216例痰涂片阳性且未接受过治疗的肺结核患者纳入本研究。这些患者被随机分为接受传统抗结核治疗（n = 117）或含Risorine的类似方案（n = 99），治疗6个月。在研究期间，定期监测症状改善、痰菌转阴和影像学改善情况。
在216例纳入研究的患者中，Risorine组75%、对照组79%完成了研究。在4周时，Risorine组的痰菌转阴率（93%）显著高于对照组（84%），且在整个研究过程中均保持这一差异。24周结束时，Risorine组的治愈率（92%）高于对照组（82%）。Risorine组有3例患者出现肝酶升高，对照组有9例患者出现肝酶升高。
Risorine是一种新型制剂，含有低剂量利福平（200毫克）、生物增强剂胡椒碱（10毫克）和标准剂量异烟肼（300毫克），与乙胺丁醇和吡嗪酰胺联合使用时，其疗效与使用传统制剂的世界卫生组织标准疗法相当。与胃肠道相比，Risorine在血液中提供更多的利福平，并且与传统利福平相比，在长期治疗中能维持更高的血药浓度，安全性更好。Risorine在强化期的痰菌转阴率更高，且一直维持到研究结束。此外，还发现新制剂Risorine在耐受性方面有更好的趋势。H = 异烟肼，R = 利福平，Z = 吡嗪酰胺，E = 乙胺丁醇
