抗结核药治疗药物监测临床应用专家共识

doi:10.3969/j.issn.1000-6621.2021.09.003

摘要/Abstract

摘要：

治疗药物监测(therapeutic drug monitoring,TDM)是通过测定患者体内的药物暴露、药理标志物或药效指标,利用定量药理模型,以药物治疗窗为基准,指导制订适合患者的个体化给药方案。抗结核治疗过程中,存在药物浓度个体差异大、不良反应多等问题,可能导致治疗失败、耐药和复发。进行抗结核药物TDM,可以优化药物治疗方案,提高药物疗效,降低不良反应。为推进中国结核病TDM规范化,保证TDM的科学性、伦理性、合法性,使患者最大程度获益,经有关结核病临床和基础研究领域的专家反复讨论,就抗结核药物TDM的意义、适应证、检测方法、实施流程及TDM的质量控制等,制订了《抗结核药治疗药物监测临床应用专家共识》。

关键词: 结核, 药物监测, 治疗应用, 指南

Abstract:

Therapeutic drug monitoring (TDM) is an individualized administration guided by determining the drug exposure, pharmacological markers or efficacy indicators in patients, by using quantitative pharmacological model and taking the drug treatment window as the benchmark. In the process of anti-tuberculosis treatment, there are many problems such as individual differences in drug concentration and various adverse effects, which may lead to treatment failure, drug resistance and recurrence. The use of anti-tuberculosis drugs TDM can optimize drug treatment, improve drug efficacy and reduce toxic and side effects. In order to promote the standardization of tuberculosis TDM in China, ensure the scientificity, ethics and legality of TDM, and maximize the benefits of patients, the Expert Consensus on the Therapeutic Drug Monitoring of Anti-Tuberculosis Drugs was composed. This consensus has been repeatedly discussed by experts in the fields of tuberculosis, including clinicians and pharmacologists. Based on the significance, indications, detection methods, implementation process and quality control of TDM, the experts generated the consensus.

Key words: Tuberculosis, Drug monitoring, Therapeutic uses, Guidebooks

首都医科大学附属北京胸科医院, 《中国防痨杂志》编辑委员会. 抗结核药治疗药物监测临床应用专家共识[J]. 中国防痨杂志, 2021, 43(9): 867-873. doi: 10.3969/j.issn.1000-6621.2021.09.003

Beijing Chest Hospital, Capital Medical University, Editorial Board of Chinese Journal of Antituberculosis. Expert consensus on the therapeutic drug monitoring of anti-tuberculosis drugs[J]. Chinese Journal of Antituberculosis, 2021, 43(9): 867-873. doi: 10.3969/j.issn.1000-6621.2021.09.003

图/表 2

表1

表2

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药品	剂量	峰浓度(C_max,mg/L)	达峰时间(T_max,h)	半衰期(T_1/2)
异烟肼	300mg/次,1次/d 900mg/次,2次/周	3~6 9~15	0.75~2.0 0.75~2.0	0.75~1.8h(快代谢型), 2.0~4.5h(慢代谢型) 0.75~1.8h(快代谢型), 2.0~4.5h(慢代谢型)
利福平	600mg/次,1次/d	8~24	1.5~2.0	2~5h
利福布汀	300mg/次,1次/d	0.45~0.9	3~4	25~36h
利福喷丁	600mg/次,1次/d^a	8~30	5~6	14~18h
乙胺丁醇	25mg·kg^-1·d^-1 50mg/kg,2次/周	2~6 4~12	2~4 2~4	双相消除2~4h,12~14h 双相消除2~4h,12~14h
吡嗪酰胺	25~35mg·kg^-1·d^-1 50mg/kg,2次/周	20~60 60~90	1~2 1~2	10~24h 10~24h
左氧氟沙星	500~1000mg/d	8~13	1~2	9h
莫西沙星	400mg/d	2.5~5	1~2	7h
环丙沙星	750mg/d	4.3	1~2	4h
加替沙星	400mg/d	2.33~3.59	1~2	7~14h
利奈唑胺	600mg/次,1次/d 300mg/次,2次/d	12~26 12~26	1.5 1.5	5~6h 5~6h
贝达喹啉	400mg/次,1次/d(前2周); 200mg/次,3次/周(2周后)	2.8~3.3(2周); 1.7(8周);1.3(24周)	4~6	5.5个月
环丝氨酸	250~500mg/d	20~35	2	15.79~25.1h
氯法齐明	100mg/次,1次/d	0.5~2	2~7	双相消除
德拉马尼	100mg/次,2次/d	1.35(开始),4.14(稳态)	4	30~38h
普托马尼	200mg/次,1次/d	1.4~2.6(开始), 2.3~4.3(稳态)	5	16h
乙硫异烟胺	250~500mg/d	2~5	1~3	2~3h
丙硫异烟胺	250~500mg/d	1~5	3	-
链霉素/卡那霉素/阿米卡星	15mg·kg^-1·d^-1 50mg/kg,2次/周	35~45 65~80	0.5~1.5肌内注射 0.5~1.5肌内注射	2~3h 2~3h
对氨基水杨酸	4000mg/d	41~68(游离酸), 76~104(钠盐)	3~4(游离酸), 0.5~1(钠盐)	2~3h

药品	剂量	有效性PK/PD参数	AUC(mg·h/L)^a	有限采样策略(h)
异烟肼	5mg·kg^-1·d^-1	AUC/MIC>567(肺)	52	1,2.5,6;1,6,8
利福平	10mg·kg^-1·d^-1	AUC/MIC>271 AUC/MIC=435~683	38.7 13	1,3,8 2,4
乙胺丁醇	25mg·kg^-1·d^-1	AUC/MIC>119	-	0,2.5,6;2,4,8
吡嗪酰胺	25~35mg·kg^-1·d^-1	AUC/MIC>8.42	363	0,2,6;0,5,8
左氧氟沙星	750~1000mg/d	AUC/MIC>119; AUC/MIC>320(耐药)	110(85~200)^b	0,5
莫西沙星	400mg/d	游离药物AUC/MIC>42; 游离药物AUC/MIC>53(耐药)	35(10~80)^b	0,1.5,6;0,6
利奈唑胺	600mg/d	游离药物AUC/MIC=119	107.5±30.16^c	0,2
贝达喹啉	400mg/次,1次/d(前2周); 200mg,3次/周	AUC_0~168h/MIC或C_均值/MIC	AUC_0~168h:187(53~689)^d	-
环丝氨酸	250~750mg/d	T>MIC30%	-	4
阿米卡星	15~20mg·kg^-1·d^-1 6.5mg·kg^-1·d^-1	C_max/MIC>75;AUC/MIC>103 C_max/MIC>20	568 113(49~232)^d	1,4 1,4
对氨基水杨酸	4000mg/d	游离药物C_min>1mg/L	-	-
链霉素	12~18mg·kg^-1·d^-1	-	197±26^c	1,6
乙硫异烟胺	250~500mg/d	AUC/MIC>56.2;游离药物 AUC/MIC=42	-	-