Programmatic Management of multidrug resistant tuberculosis (MDR TB) services were introduced in the Indian TB control programme in 2007. A pharmacokinetic (PK) study of drugs used to treat MDR TB, namely levofloxacin (LFX), ethionamide (ETH), cycloserine (CS), pyrazinamide (PZA), moxifloxacin (MFX) and isoniazid (INH) was undertaken in adult MDR TB patients treated according to the prevailing guidelines in India. Factors influencing drug PK and end-of-intensive phase (IP) status were also determined. We recruited 350 MDR TB patients receiving anti-TB treatment (ATT) in the Indian Government programme in south India. At steady state, serial blood samples were collected, after supervised drug administration. Status at end of IP was noted from the programme records. Of the 303 patients for whom end-of-IP status was known, 214 were culture negative (responders), while 45 patients were either culture positive or required change of regimen or had died before completion of IP (non-responders). The median C_max (2.0 vs 2.9µg/ml; p = 0.005) and AUC_0-12 (12.2 vs 17.0µg/ml.h; p = 0.002) of ETH were significantly lower in non-responders than responders at IP. In multivariate logistic regression analysis, after excluding defaulters and adjusting for confounders, AUC_0-12 of ETH significantly influenced end-of-IP status (aOR - 1.065; 95% CI: 1.001 - 1.134; p = 0.047). Drug doses used currently in the programme produced optimal drug concentrations in majority of patients. ETH played a major role in the MDR TB combination regimen and was a key determinant of end-of-IP status.

中文翻译：

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印度耐多药结核病患者抗结核药的药代动力学

2007年，印度结核病控制规划引入了耐多药结核病（MDR TB）服务的程序化管理。对用于治疗MDR TB的药物，即左氧氟沙星（LFX），乙乙酰胺（ETH），环丝氨酸（CS）的药代动力学（PK）研究），吡嗪酰胺（PZA），莫西沙星（MFX）和异烟肼（INH）用于根据印度现行指南治疗的成年耐多药结核病患者。还确定了影响药物PK和强化后期（IP）状态的因素。我们在印度南部的印度政府计划中招募了350名接受抗结核治疗（ATT）的耐多药结核病患者。在监督下给药后，在稳定状态下收集系列血样。从计划记录中注意到IP末尾的状态。在303名知悉IP终止状态的患者中，214例培养阴性（响应者），而45例培养阳性或需要改变治疗方案或在IP完成前死亡（无响应）。中位数C在IP中，无响应者的ETH的_最大值（2.0 vs. 2.9µg / ml； p = 0.005）和AUC _0-12（12.2 vs 17.0µg / ml.h； p = 0.002）显着低于IP响应者。在多变量logistic回归分析中，在排除默认值并调整混杂因素后，ETH的AUC _0-12显着影响IP终结状态（aOR-1.065； 95％CI：1.001- 1.134； p = 0.047）。该程序中当前使用的药物剂量在大多数患者中产生最佳药物浓度。ETH在耐多药结核病合并方案中发挥了重要作用，并且是IP终结状态的关键决定因素。