李阳;吴琼;

• 1:中国医科大学附属盛京医院药学部
• 2:中国医科大学附属盛京医院小儿神经内科

摘要(Abstract)：

吡嗪酰胺是抗结核治疗一线药物,但具体的抗结核菌机制尚不明确,已有研究发现,吡嗪酰胺在酸性及厌氧条件下具有特殊抗结核杆菌机制。由于吡嗪酰胺的高效杀菌作用以及协同其他药物发挥较高的抗结核杆菌的效果,加之其可适用于肺结核全程治疗,目前已被广泛用于抗结核治疗,但这导致吡嗪酰胺耐药增加的现象。此外,吡嗪酰胺引起的肝损害作为药物常见的毒副作用也应引起重视。本文就吡嗪酰胺在肺结核患者治疗中的机制、效果、安全性及其与其他药物联合应用的情况进行了综述。

关键词(KeyWords)： 肺结核;吡嗪酰胺;机制;耐药

Abstract:

Keywords:

基金项目(Foundation): 辽宁省博士科研启动基金计划项目(2019-BS-280)

作者(Authors): 李阳;吴琼;

DOI: 10.14053/j.cnki.ppcr.202108019

参考文献(References)：

• [1] Pezzella AT.History of pulmonary tuberculosis[J].Thorac Surg Clin,2019,29(1):1-17.
• [2] 何畏，鲁小莉，吴桂辉.吡嗪酰胺耐药对初治菌阳肺结核患儿疗效的影响[J].安徽医药，2018,22(5):958-961.
• [3] Lee M,Mok J,Kim DK,et al.Delamanid,linezolid,levofloxacin,and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs,MDR-END):study protocol for a phase II/III,multicenter,randomized,open-label clinical trial[J].Trials,2019,20(1):57.
• [4] DOTS Expansion Working Group,World Health Organization,Stop TB Partnership.DOTS Expansion Working Group strategic plan,2006-2015[J].New Zealand Geographer,2006,15(8):96-98.
• [5] 陈明，吴珂，吴首蓉，等.结核患者血清尿酸与吡嗪酰胺血药浓度关系研究[J].中国药物应用与监测，2018,1(5):274-276.
• [6] Miotto P,Zhang Y,Cirillo DM,et al.Drug resistance mechanisms and drug susceptibility testing for tuberculosis[J].Respirology,2018,23(12):1098-1113.
• [7] Njire M,Tan Y,Mugweru J,et al.Pyrazinamide resistance in mycobacterium tuberculosis:review and update[J].Adv Med Sci,2016,61(1):63-71.
• [8] Rehman AU,Khan MT,Liu H,et al.Exploring the pyrazinamide drug resistance mechanism of clinical mutants T370P and W403G in ribosomal protein S1 of mycobacterium tuberculosis[J].J Chem Inf Model,2019,59(4):1584-1597.
• [9] Donald PR,Maritz JS,Diacon AH.Pyrazinamide pharmacokinetics and efficacy in adults and children[J].Tuberculosis (Edinb),2012,92(1):1-8.
• [10] 王玉，李忠红，张正行，等.拉曼光谱在药物分析中的应用[J].药学学报，2004,39(9):764-768.
• [11] 谢闯，郝菁，常芯瑗，等.吡嗪酰胺-2,5-二羟基苯甲酸共晶制备及过程在线研究[J].天津大学学报：自然科学与工程技术版，2019,52(1):13-19.
• [12] 陈曦，刘忠泉，王彬，等.14种抗结核药物在巨噬细胞内的抗结核活性评价[J].中国防痨杂志，2019,41(9):993-998.
• [13] 罗成玲，邓燕，杜先智.结核杆菌耐氟喹诺酮类和吡嗪酰胺的分子机制研究进展[J].国际呼吸杂志，2016,36(14):1102-1104.
• [14] 黄盛晶，饶运帷，谭守勇.吡嗪酰胺耐药对初治菌阳肺结核复发的影响[J].实用医学杂志，2016,32(13):2224-2226.
• [15] Gopal P,Grüber G,Dartois V,et al.Pharmacological and meolecular mechanisms behind the sterilizing activity of pyrazinamide[J].Trends Pharmacol Sci,2019,40(12):930-940.
• [16] Scorpio A,Zhang Y.Mutation in pncA,a gene encoding pyrazinamidase/ nicotinamidase,cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus[J].Nat Med,1996,2(6):662-667.
• [17] 牛宁奎，马涛，王自立，等.异烟肼、利福平、吡嗪酰胺三联抗结核药/表皮转化生长因子-β1 siRNA纳米脂质体体外细胞毒性作用及机制研究[J].中国感染与化疗杂志，2018,18(6):592-598.
• [18] Corrêa MF,Fernandes JP.Pyrazinamide and pyrazinoic acid derivatives directed to mycobacterial enzymes against tuberculosis[J].Curr Protein Pept Sci,2016,17(3):213-219.
• [19] Rawat A,Chaturvedi S,Singh AK,et al.Metabolomics approach discriminates toxicity index of pyrazinamide and its metabolic products,pyrazinoic acid and 5-hydroxy pyrazinoic acid[J].Hum Exp Toxicol,2018,37(4):373-389.
• [20] 张阳奕，江渊，武洁，等.实验室检测结核分枝杆菌对吡嗪酰胺耐药性的方法学评价[J].检验医学，2018,33(4):326-330.
• [21] Garhyan J,Bhuyan S,Pulu I,et al.Preclinical and clinical evidence of mycobacterium tuberculosis persistence in the hypoxic Niche of bone marrow mesenchymal stem cells after therapy[J].Am J Pathol,2015,185(7):1924-34.
• [22] 张洁，齐红伟，丁北川，等.结核分枝杆菌临床分离株对吡嗪酰胺的药物敏感性分析[J].现代检验医学杂志，2017,32(3):49-51.
• [23] Srivastava S1,Deshpande D1,Magombedze G1,et al.Efficacy versus hepatotoxicity of high-dose rifampin,pyrazinamide,and moxifloxacin to shorten tuberculosis therapy duration:there is still fight in the old warriors yet[J].Send to Clin Infect Dis,2018,67(suppl_3):S359-S364.
• [24] Velásquez GE,Calderon RI,Mitnick CD,et al.Pyrazinamide resistance assays and two-month sputum culture status in patients with multidrug-resistant tuberculosis[J].Antimicrob Agents Chemother,2016,60(11):6766-6773.
• [25] 吴璇，王勃，毛晓辉，等.左氧氟沙星与吡嗪酰胺治疗肺结核合并糖尿病的临床比较[J].药物评价研究，2016,39(4):660-663.
• [26] 朱慧，王彬，付雷，等.吡嗪酰胺每日一次与三次给药在小鼠体内的药代动力学比较及其对异烟肼-利福平的影响[J].中国防痨杂志，2013,35(12):983-987.
• [27] Liu J,Shi W,Zhang S,et al.Mutations in efflux pump rv1258c (tap) cause resistance to pyrazinamide,isoniazid,and streptomycin in M.tuberculosis[J].Front Microbiol,2019,19(10):216.
• [28] 朱敏，陈园园，鲍志坚.含莫西沙星及吡嗪酰胺超短程化疗方案对菌阳肺结核初治的效果分析[J].国际流行病学传染病学杂志，2019,46(2):107-111.
• [29] 邓彬，刘海燕，孙纪英，等.胸腺肽联合吡嗪酰胺治疗耐多药肺结核的近、中期疗效及对免疫功能的影响[J].检验医学与临床，2018,15(2):209-212,216.
• [30] 叶璐，甘能金.左旋氧氟沙星与吡嗪酰胺治疗肺结核合并2型糖尿病近期疗效及安全性分析[J].临床肺科杂志，2017,22(9):1659-1662.
• [31] Zhang Y,Yew WW.Mechanisms of drug resistance in mycobacterium tuberculosis:update 2015.[J].Int J Tuberc Lung Dis,2015,19(11):1276-1289.
• [32] den Hertog AL,Sengstake S,Anthony RM2.Pyrazinamide resistance in mycobacterium tuberculosis fails to bite[J].Pathog Dis,2015,73(6):ftv037.
• [33] 高慧，施理，吴涛，等.吡嗪酰胺联合左氧氟沙星对耐多药肺结核的治疗效果及对患者生活质量的影响[J].中国医药，2020,15(2):216-220.
• [34] 罗雪丽.异烟肼联合吡嗪酰胺治疗老年结核性脑膜炎50例及心理护理[J].中国药业，2013,22(21):90-91.
• [35] Stemkens R,Litjens CHC,Dian S,et al.Pharmacokinetics of pyrazinamide during the initial phase of tuberculous meningitis treatment[J].Int J Antimicrob Agents,2019,54(3):371-374.
• [36] 罗振华，钱雪琴，范齐文，等.结核分枝杆菌吡嗪酰胺耐药相关分子特征分析[J].中华微生物学和免疫学杂志，2015,27(9):660-665.
• [37] Juma SP,Maro A,Pholwat S,et al.Underestimated pyrazinamide resistance may compromise outcomes of pyrazinamide containing regimens for treatment of drug susceptible and multi-drug-resistant tuberculosis in Tanzania[J].BMC Infect Dis,2019,19(1):129.
• [38] 吴碧彤，邝浩斌，刘志辉，等.标准耐多药结核病化疗方案中是否对吡嗪酰胺耐药的疗效对比研究[J].中国防痨杂志，2019,41(4):447-451.
• [39] Bouazzi OE,Hammi S,Bourkadi JE,et al.First line anti-tuberculosis induced hepatotoxicity:incidence and risk factors[J].Pan Afr Med J,2016,9(25):167.
• [40] 覃红娟，谭守勇，邝浩斌，等.吡嗪酰胺与抗结核药物肝损伤的相关性[J].实用医学杂志，2016,32(12):1948-1951.
• [41] Zhao H,Si ZH,Li MH,et al.Pyrazinamide-induced hepatotoxicity and gender differences in rats as revealed by a 1H NMR based metabolomics approach[J].Toxicol Res (Camb),2016,6(1):17-29.
• [42] 田涛，谢红东，陈明贵，等.抗结核药物诱导肝损伤后三种不同再次给药方案的比较研究[J].临床肺科杂志，2016,21(2):303-306.
• [43] 韩冰，胡柳杨，姚亚超，等.合并糖尿病的结核病患者接受吡嗪酰胺治疗后高尿酸血症、痛风性关节炎发病情况观察[J].山东医药，2020,60(3):60-62.
• [44] 刘硕，张昕，次卓嘎，等.2012-2018年首都医科大学附属北京胸科医院吡嗪酰胺致不良反应分析[J].现代药物与临床，2019,34(5):1574-1577.
• [45] Sharma R,Battu P,Singla M,et al.Expression profile of markers of oxidative stress,injury and apoptosis in anti-tuberculosis drugs induced nephrotoxicity[J].Nephrology (Carlton),2019,24(7):689-695.