Department of Medicine, University of Cape Town, Cape Town, South Africa.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
J Antimicrob Chemother. 2024 Aug 1;79(8):2022-2030. doi: 10.1093/jac/dkae206.
In South Africa, an estimated 11% of the population have high alcohol use, a major risk factor for TB. Alcohol and other substance use are also associated with poor treatment response, with a potential mechanism being altered TB drug pharmacokinetics.
To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB.
We prospectively enrolled participants ≥15 years old, without HIV, and initiating drug-susceptible TB treatment in Worcester, South Africa. Alcohol use was measured via self-report and blood biomarkers. Other illicit substances were captured through a urine drug test. Plasma samples were drawn 1 month into treatment pre-dose, and 1.5, 3, 5 and 8 h post-dose. Non-linear mixed-effects modelling was used to describe the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol. Alcohol and drug use were tested as covariates.
The study included 104 participants, of whom 70% were male, with a median age of 37 years (IQR 27-48). Alcohol use was high, with 42% and 28% of participants having moderate and high alcohol use, respectively. Rifampicin and isoniazid had slightly lower pharmacokinetics compared with previous reports, whereas pyrazinamide and ethambutol were consistent. No significant alcohol use effect was detected, other than 13% higher ethambutol clearance in participants with high alcohol use. Methaqualone use reduced rifampicin bioavailability by 19%.
No clinically relevant effect of alcohol use was observed on the pharmacokinetics of first-line TB drugs, suggesting that poor treatment outcome is unlikely due to pharmacokinetic alterations. That methaqualone reduced rifampicin means dose adjustment may be beneficial.
在南非，约有 11%的人口存在高酒精使用量的情况，这是结核病的主要危险因素之一。酒精和其他物质的使用也与治疗反应不佳有关，其潜在机制可能是改变了结核病药物的药代动力学。
研究酒精和非法物质使用对肺结核患者一线抗结核药物药代动力学的影响。
我们前瞻性地招募了年龄在 15 岁及以上、无 HIV 且正在接受药物敏感结核病治疗的参与者，这些参与者在南非伍斯特。通过自我报告和血液生物标志物来测量酒精使用情况。其他非法物质则通过尿液药物测试来捕获。在治疗开始后 1 个月时，以及服药后 1.5、3、5 和 8 小时抽取血浆样本。采用非线性混合效应模型来描述利福平、异烟肼、吡嗪酰胺和乙胺丁醇的药代动力学。将酒精和药物使用作为协变量进行测试。
该研究纳入了 104 名参与者，其中 70%为男性，中位年龄为 37 岁（IQR 27-48）。酒精使用量较高，分别有 42%和 28%的参与者存在中度和高度酒精使用情况。与之前的报告相比，利福平和异烟肼的药代动力学略低，而吡嗪酰胺和乙胺丁醇则保持一致。除了高酒精使用组的乙胺丁醇清除率增加 13%外，未发现酒精使用有显著影响。美沙酮的使用使利福平的生物利用度降低了 19%。
在一线抗结核药物的药代动力学方面，未观察到酒精使用的临床相关影响，这表明治疗效果不佳不太可能是由于药物代谢改变所致。美沙酮降低了利福平的生物利用度，这意味着可能需要调整剂量。
