PDF(Pubmed)
Abstract：
BACKGROUND: 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.
OBJECTIVE: To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB.
METHODS: 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.
RESULTS: 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%.
CONCLUSIONS: 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.
OBJECTIVE: To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB.
METHODS: 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.
RESULTS: 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%.
CONCLUSIONS: 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.
摘要：
背景：在南非，估计有11%的人口使用大量酒精，结核病的主要危险因素。酒精和其他物质的使用也与不良的治疗反应有关，潜在的机制是改变结核病药物的药代动力学。
目的：研究酒精和非法药物使用对肺结核患者一线结核药物药代动力学的影响。
方法：我们前瞻性招募≥15岁的参与者，没有艾滋病毒，并在伍斯特开始药物敏感的结核病治疗，南非。通过自我报告和血液生物标志物来测量酒精的使用。通过尿液药物测试捕获了其他非法物质。在治疗前1个月抽取血浆样本，和1.5，3，5和8小时后的剂量。非线性混合效应模型用于描述利福平的药代动力学，异烟肼,吡嗪酰胺和乙胺丁醇。酒精和药物使用作为协变量进行测试。
结果：该研究包括104名参与者，其中70%是男性，年龄中位数为37岁（IQR27-48）。酒精使用率很高，42%和28%的参与者有中度和高度饮酒，分别。利福平和异烟肼的药代动力学略低于以前的报道，而吡嗪酰胺和乙胺丁醇是一致的。未检测到明显的酒精使用效果,在高酒精使用的参与者中，乙胺丁醇清除率高于13%。使用甲喹酮将利福平的生物利用度降低了19%。
结论：未观察到酒精使用对一线结核病药物的药代动力学的临床相关影响，提示不良的治疗结果不太可能是由于药代动力学改变.甲喹酮减少利福平意味着剂量调整可能是有益的。
目的：研究酒精和非法药物使用对肺结核患者一线结核药物药代动力学的影响。
方法：我们前瞻性招募≥15岁的参与者，没有艾滋病毒，并在伍斯特开始药物敏感的结核病治疗，南非。通过自我报告和血液生物标志物来测量酒精的使用。通过尿液药物测试捕获了其他非法物质。在治疗前1个月抽取血浆样本，和1.5，3，5和8小时后的剂量。非线性混合效应模型用于描述利福平的药代动力学，异烟肼,吡嗪酰胺和乙胺丁醇。酒精和药物使用作为协变量进行测试。
结果：该研究包括104名参与者，其中70%是男性，年龄中位数为37岁（IQR27-48）。酒精使用率很高，42%和28%的参与者有中度和高度饮酒，分别。利福平和异烟肼的药代动力学略低于以前的报道，而吡嗪酰胺和乙胺丁醇是一致的。未检测到明显的酒精使用效果,在高酒精使用的参与者中，乙胺丁醇清除率高于13%。使用甲喹酮将利福平的生物利用度降低了19%。
结论：未观察到酒精使用对一线结核病药物的药代动力学的临床相关影响，提示不良的治疗结果不太可能是由于药代动力学改变.甲喹酮减少利福平意味着剂量调整可能是有益的。
