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中国防痨杂志 ›› 2018, Vol. 40 ›› Issue (7): 744-749.doi: 10.3969/j.issn.1000-6621.2018.07.014

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  1. 101149 首都医科大学附属北京胸科医院 北京市结核病胸部肿瘤研究所 耐药结核病研究北京市重点实验室 药物学研究室(郭少晨、朱慧、王彬、刘忠泉、徐建、付雷、陆宇),结核科(郭超、陈效友);
  • 收稿日期:2018-01-02 出版日期:2018-07-10 发布日期:2018-09-07
  • 通信作者: 陈效友,陆宇;
  • 基金资助:

Analysis of plasma concentrations of first-line anti-tuberculosis drugs in 909 tuberculosis patients

Shao-chen GUO,Hui ZHU,Chao GUO,Bin WANG,Zhong-quan LIU,Jian XU,Lei FU,Xiao-you CHEN(),Yu LU()   

  1. Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
  • Received:2018-01-02 Online:2018-07-10 Published:2018-09-07
  • Contact: Xiao-you CHEN,Yu LU;


目的 分析结核病患者一线抗结核药物血药浓度监测情况。方法 选取2010年1月至2016年11月于首都医科大学附属北京胸科医院住院并进行一线抗结核药物血药浓度测定者作为研究对象,共909例;其中,服用INH者909例,服用EMB者783例,服用PZA者587例,服用RFP者503例。患者服药剂量:INH 300mg/d、RFP 450mg/d或600mg/d、PZA 1500mg/d、EMB 750mg/d。收集研究对象性别、年龄、并发糖尿病情况,以及血药浓度监测结果,并进行分析。结果 服用INH、EMB、PZA和RFP(450mg/d和600mg/d)2h后,患者血药浓度低于目标浓度范围者分别占57.3%(521/909)、82.2%(644/783)、29.8%(175/587)、51.6%(190/368)和36.3%(49/135)。其中,男性患者中INH、EMB、PZA、RFP(450mg/d)出现低血药浓度者分别占67.2%(396/589)、85.9%(451/525)、39.9%(153/383)、60.0%(135/225),均高于女性患者[39.1%(125/320)、74.8%(193/258)、10.8%(22/204)、38.5%(55/143)],差异均有统计学意义(χ 2值分别为67.26、14.59、54.10、16.24,P值均<0.01)。体质量≥50kg的患者,INH、EMB、PZA、RFP(450mg/d)出现低血药浓度者分别占61.7%(428/694)、83.3%(513/616)、35.3%(159/451)、55.6%(154/277),均高于体质量<50kg者[30.3%(40/132)、72.4%(76/105)、4.7%(4/86)、37.1%(23/62)],差异均有统计学意义(χ 2值分别为44.44、7.12、32.00、6.95,P值均<0.05)。结核病并发糖尿病患者,INH和PZA出现低血药浓度者分别占72.6%(143/197)和53.8%(71/132),高于未并发糖尿病者[53.1%(378/712)和22.9%(104/455)],差异均有统计学意义(χ 2值分别为23.98和46.78,P值均<0.01)。 结论 结核病患者服用一线抗结核药物后出现低血药浓度情况较为普遍,患者性别、体质量、并发症等因素均会影响其血药浓度水平;提示开展一线抗结核药物血药浓度监测工作,并根据患者个体情况调整治疗方案对结核病治疗是必要的。

关键词: 结核, 药物监测, 药代动力学, 利福平, 异烟肼, 乙胺丁醇, 吡嗪酰胺


Objective This study aimed to analyze the plasma concentrations of first-line anti-tuberculosis drugs in tuberculosis patients.Methods A total of 909 patients (909 for isoniazid (INH), 783 for ethambutol (EMB), 587 for pyrazinamide (PZA), and 503 for rifampin (RFP)), who admitted to Beijing Chest Hospital Affilia-ted to Capital Medical University from January 2010 to November 2016 and initiated a daily first-line regimen for treatment of tuberculosis, were selected as the subjects of this study. The doses of medicine were: INH 300 mg/d; RFP 450 mg/d or 600 mg/d; PZA 1500 mg/d; or EMB 750 mg/d. Basic information including gender, age and comorbidity and concentrations of INH, EMB, PZA and RFP were collected and analyzed.Results 57.3% (521/909, INH), 82.2% (644/783, EMB), 29.8% (175/587, PZA), 51.6% (190/368, RFP 450 mg/d) and 36.3% (49/135, RFP 600 mg/d) cases had a C2h lower than the reference ranges. 67.2% (396/589), 85.9% (451/525), 39.9% (153/383) and 60.0% (135/225) of male patients had a C2h lower than the reference ranges of these drugs (INH, EMB, PZA and RFP 450 mg/d), which were significantly higher than the counterparts of female cases (39.1% (125/320), 74.8% (193/258), 10.8% (22/204) and 38.5% (55/143)). The differences were statistically significant (χ 2=67.26, 14.59, 54.10 and 16.24; Ps<0.01). 61.7% (428/694), 83.3% (513/616), 35.3% (159/451) and 55.6% (154/277) of cases with body weight ≥50 kg had a C2h lower than the reference ranges of drugs (INH, EMB, PZA and RFP 450 mg/d), which were significantly higher than the counterparts of those with body weight <50 kg (30.3% (40/132), 72.4% (76/105), 4.7% (4/86) and 37.1% (23/62)). The differences were statistically significant (χ 2=44.44, 7.12, 32.00 and 6.95; Ps<0.05). Low plasma drug concentration of INH and PZA often occurred in cases with diabetes mellitus, with a proportion of 72.6% (143/197) and 53.8% (71/132), compared with those without diabetes mellitus (53.1% (378/712) and 22.9% (104/455)). The differences were statistically significant (χ 2=23.98 and 46.78; Ps<0.01). Conclusion It is common that tuberculosis patients have low blood drug concentrations after taking first-line anti-tuberculosis drugs. The individual’s situation varies with several factors including gender, body weight and comorbidity. The monitoring of blood concentration of first-line anti-tuberculosis drugs should be carried out, and modification of treatment plans based on individual’s conditions is essential for therapeutic goals.

Key words: Tuberculosis, Drug monitoring, Pharmacokinetics, Rifampin, Isoniazid, Ethambutol, Pyrazinamide