宿主N-乙酰转移酶2多态性与异烟肼诱导肝损伤相关性的研究进展  

Association between isoniazid induced hepatotoxicity and host N-acetyltransferase 2 polymorphisms

作　　者：杨松[1] 郭建琼 严晓峰[1] 唐神结[3] Yang Song;Guo Jianqiong;Yan Xiaofeng;Tang Shenjie(Research Institute of Tuberculosis,Chongqing Public Health Medical Center,Chongqing 400036,China;Infectious Disease Department,the First Affiliated Hospital of Army Medical University,Chongqing 400032,China;Beijing Chest Hospital,Capital Medical University,Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing 101149,China)

机构地区：[1]重庆市公共卫生医疗救治中心结核病研究室,重庆400036 [2]陆军军医大学第一附属医院感染科,重庆400032 [3]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,北京101149

出　　处：《中华结核和呼吸杂志》2022年第2期227-232,共6页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：重庆市卫生健康委员会、重庆市科学技术局联合医学科研计划(2019ZDXM035)。

摘　　要：异烟肼作为一种治疗敏感结核病近70年的主要药物,其药物动力学差异可影响其吸收,低血药浓度导致低疗效;反之高浓度可导致肝损伤或死亡。引起血药浓度波动的因素包括异烟肼吸收(如药物-药物、药物-食物相互作用,胃肠疾病,糖尿病或结核病等疾病状态)和肝酶代谢的异常等。N-乙酰转移酶2(N-acetyltransferase 2)基因(NAT2)型及蛋白酶(NAT2)表型的多态性显著影响血浆异烟肼浓度。目前缺乏异烟肼治疗引起的药物不良反应处理指南,针对出现的异烟肼不良反应仅基于临床经验采取突然停药或降低异烟肼剂量,但这样的措施可导致结核分枝杆菌耐药性产生。故进一步明确宿主NAT2基因型及其表型多态性、血浆异烟肼浓度和不良反应的相关性有助于提高疗效和将不良反应减少到最低程度。Isoniazid(INH,H)has been a key drug for treating drug-susceptible tuberculosis(TB)for nearly seventy years.The differences in the pharmacokinetic(PK)might affect INH absorption.Low plasma concentration is related to less treatment outcomes and vice versa,but higher plasma concentrations can induce hepatotoxicity or death.Factors that can cause fluctuations in blood concentration include INH absorption(i.e.drug-drug or drug-food interactions and other diseases such as gastrointestinal problems,diabetes or TB)and abnormal metabolization by the liver.N-acetyltransferase 2(NAT2)genetic polymorphism significantly affects the plasma concentrations of INH.However,there is a lack of guidelines for the management of adverse drug reactions caused by isoniazid therapy,and the only measures taken to address adverse reactions to isoniazid are abrupt discontinuation of the drug or reduction in the dose of isoniazid based on clinical experience,but such measures could lead to the development of drug resistance in Mycobacterium tuberculosis.Therefore,further clarification of the correlation between the host NAT2 genotype and its phenotypic polymorphisms,plasma isoniazid concentration and adverse effects can help to improve the efficacy and minimize the adverse effects.

关 键 词：酶代谢 药物动力学 NAT2 胃肠疾病 血药浓度 异烟肼 肝损伤 疾病状态 

分 类 号：R575[医药卫生—消化系统]