Email Alert | RSS    帮助

中国防痨杂志 ›› 2018, Vol. 40 ›› Issue (2): 157-160.doi: 10.3969/j.issn.1000-6621.2018.02.009

• 论著 • 上一篇    下一篇



  1. 200040 上海,复旦大学附属华山医院感染科(刘其会、孙峰、张文宏);上海市公共卫生临床中心Ⅰ期临床试验中心(孙涛、贾小芳、张丽军);温州市中心医院感染科(苏菲菲、施伎蝉、蒋贤高)
  • 收稿日期:2018-01-16 出版日期:2018-02-10 发布日期:2018-03-14
  • 通信作者: 刘其会

The relationship between plasma concentrations of the first-line anti-tuberculosis drugs and sputum negative conversion at early stage

Qi-hui LIU,Feng SUN,Tao SUN,Xiao-fang JIA,Fei-fei SU,Ji-chan SHI,Li-jun ZHANG,Xian-gao JIANG(),Wen-hong. ZHANG   

  1. *Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
  • Received:2018-01-16 Online:2018-02-10 Published:2018-03-14
  • Contact: Qi-hui LIU

摘要: 目的





72例研究对象中1例患者痰培养结果为耐多药肺结核,1例失访,最终纳入70例进行分析。其中,菌阴肺结核患者16例,菌阳肺结核患者54例。研究对象服药1周达到稳态药物浓度后进行采血检测,25.7%(18/70)的患者R的峰值浓度(Cmax)低于推荐范围(<8μg/ml),38.6%(27/70)的患者H的Cmax低于推荐范围(<3μg/ml),65.7%(46/70)的患者E的Cmax低于推荐范围(<2μg/ml)。54例菌阳肺结核患者抗结核药物治疗2个月末,48例痰菌阴转,6例未阴转。痰菌阴转者血浆中E服药后2h浓度(C2h)、Cmax、服药后8h曲线下面积(AUC0~8)值分别为(1.81±0.91)μg/ml、(1.81±0.85)μg/ml、(7.67±3.25)μg·h·ml -1,高于痰菌未阴转者[C2hCmax、AUC0~8分别为(0.93±0.32)μg/ml、(1.06±0.25)μg/ml、(4.93±0.72)μg·h·ml -1],差异有统计学意义(t=4.74,P<0.01;t=4.93,P<0.01;t=4.95,P<0.01);痰菌阴转者血浆中H的C2hCmax值分别为(3.67±1.64)μg/ml、(3.85±1.59)μg/ml,均高于痰菌未阴转者[C2hCmax分别为(2.11±1.14)μg/ml、(2.11±1.14)μg/ml],差异有统计学意义(t=2.60,P=0.012;t=2.25,P=0.029)。



关键词: 利福平, 异烟肼, 乙胺丁醇, 药代动力学, 前瞻性研究

Abstract: Objective

To study the pharmacokinetics of the first-line anti-tuberculosis drugs including rifampicin, isoniazid, and ethambutol in a cohort of Chinese patients with tuberculosis and to determine the relationship between the pharmacokinetic parameters of these anti-tuberculosis drugs and the clinical treatment outcomes.


A prospective study was conducted to recruit patients diagnosed with pulmonary tuberculosis from the Inpatient Department of the Wenzhou Central Hospital from October 1, 2015 to January 31, 2016. A total of 72 patients were enrolled. Subjects were initially treated or retreated once, and both bacteriologically confirmed and clinically diagnosed cases were eligible. Plasma samples were collected 0.5h before and 2h, 4h, 6h, 8h after taking standard quadruple drugs for one week doses. Plasma concentrations were determined using LC-MS/MS. Patients were followed up 2 months after the initiation of treatment to assess the relationships between sputum negative conversion and plasma concentrations.


Among the 72 patients, one patient was confirmed to have multidrug-resistant tuberculosis and one patient was lost to follow up. Thus, 70 patients were analyzed at last, among whom 16 patients were bacteriologically negative and 54 patients were bacteriologically positive at initial diagnosis. The plasma exposures at steady state after one week of drug administration were analyzed. 25.7% (18/70) patients had a plasma peak concentration (Cmax) of rifampicin lower than the recommended range (<8μg/ml), 38.6% (27/70) cases had a Cmax of isoniazid lower than the recommended range (<3μg/ml), whereas 65.7% (46/70) patients had a Cmax of ethambutol lower than the recommended range (<2μg/ml). After 2-month of treatment, among the 54 patients who were sputum bacteria positive at initial diagnosis, 48 patients conversed to sputum bacteria negative, while sputum bacteria were still detected in 6 patients. The C2h, Cmax, and AUC0-8 of ethambutol were significantly higher in patients who got sputum conversion after 2-month of treatment ((1.81±0.91)μg/ml, (1.81±0.85)μg/ml, and (7.67±3.25)μg·h·ml -1) compared with those who failed to get sputum conversion ((0.93±0.32)μg/ml, (1.06±0.25)μg/ml, and (4.93±0.72)μg·h·ml -1) (t=4.74, P<0.01; t=4.93, P<0.01; and t=4.95, P<0.01, respectively). The C2h and Cmax of isoniazid were significantly higher in patients who got sputum conversion after 2-month of treatment ((3.67±1.64)μg/ml and (3.85±1.59)μg/ml) compared with those who failed to get sputum conversion ((2.11±1.14)μg/ml and (2.11±1.14)μg/ml) (t=2.60, P=0.012; t=2.25, P=0.029, respectively).


The Cmax of drugs below the recommended reference ranges, especially isoniazid and ethambutol, were observed in some patients with pulmonary tuberculosis. The dosage of isoniazid and ethambutol may need to be modified. In addition, the sputum negative conversion after 2-month of treatment was shown to be related with the serum concentration of isoniazid and ethambutol.

Key words: Rifampin, Isoniazid, Ethambutol, Pharmacokinetics, Prospective studies