Tappero Jordan W, Bradford Williamson Z, Agerton Tracy B, Hopewell Philip, Reingold Arthur L, Lockman Shahin, Oyewo Aderonke, Talbot Elizabeth A, Kenyon Thomas A, Moeti Themba L, Moffat Howard J, Peloquin Charles A
Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Clin Infect Dis. 2005 Aug 15;41(4):461-9. doi: 10.1086/431984. Epub 2005 Jul 8.
We conducted a pharmacokinetic study of antimycobacterial drugs involving a cohort of patients with pulmonary tuberculosis (TB) in Gaborone, Botswana, to assess the prevalence of and risk factors for low drug concentrations in serum.
Adults participated if they had a history of cough > or =2 weeks, had abnormal chest radiograph findings, consented to testing for human immunodeficiency virus (HIV), had sputum cultures positive for Mycobacterium tuberculosis, and were receiving antituberculous therapy for >7 days. Observed maximum serum concentrations were compared with published normal ranges. RESULTS. Of 91 patients enrolled, 89 (98%) were outpatients, and 59 (68%) of 87 patients tested had HIV infection. The following numbers of patients had low serum concentrations of the following drugs: isoniazid, 27 (30%) of 90; rifampin, 71 (78%) of 91; ethambutol, 37 (41%) of 91; and pyrazinamide, 1 (1%) of 91. Low serum concentrations of both isoniazid and rifampin occurred in 23 (26%) of 90 patients. Low serum concentrations of rifampin were found in both HIV-infected and non-HIV-infected patients, and such patients were less likely to have >4 weeks of symptoms, more likely to have lymphadenopathy, and more likely to have low serum albumin levels (P<.05 for all). The associations with noncavitary pulmonary disease (P=.12) and HIV infection (P=.07) did not reach statistical significance. Delayed absorption was most common with ethambutol, followed by rifampin.
These data, predominantly from HIV-infected patients with TB, suggest that low isoniazid, rifampin, and ethambutol concentrations are common in Botswana. In contrast, pyrazinamide usually is well absorbed.
我们在博茨瓦纳哈博罗内对一组肺结核（TB）患者进行了抗分枝杆菌药物的药代动力学研究，以评估血清中药物浓度低的患病率及危险因素。
成年患者若有咳嗽≥2周的病史、胸部X线检查结果异常、同意接受人类免疫缺陷病毒（HIV）检测、痰培养结核分枝杆菌呈阳性且接受抗结核治疗超过7天，则可参与研究。将观察到的血清最大浓度与已公布的正常范围进行比较。
在91名登记患者中，89名（98%）为门诊患者，87名接受检测的患者中有59名（68%）感染了HIV。以下是血清中以下药物浓度低的患者数量：异烟肼，90名患者中有27名（30%）；利福平，91名患者中有71名（78%）；乙胺丁醇，91名患者中有37名（41%）；吡嗪酰胺，91名患者中有1名（1%）。90名患者中有23名（26%）异烟肼和利福平的血清浓度均低。在HIV感染患者和未感染HIV的患者中均发现利福平血清浓度低，且这类患者出现症状超过4周的可能性较小，出现淋巴结病的可能性较大，血清白蛋白水平较低的可能性较大（所有P值均<0.05）。与非空洞性肺病（P = 0.12）和HIV感染（P = 0.07）的关联未达到统计学显著性。乙胺丁醇吸收延迟最为常见，其次是利福平。
这些主要来自感染HIV的TB患者的数据表明，在博茨瓦纳，异烟肼、利福平和乙胺丁醇浓度低很常见。相比之下，吡嗪酰胺通常吸收良好。
