结核病患者N-乙酰基转移酶2编码基因多态性检测与异烟肼合理用药专家共识

异烟肼是抗结核化疗方案中的核心药物,其在人体内的代谢速度取决于N-乙酰基转移酶2(N-acetyltransferase-2,NAT2)活性,而依据其编码基因NAT2的多态性可将人群分为快乙酰化型、中间乙酰化型和慢乙酰化型。不同乙酰化类型患者服用相同剂量异烟肼后的血药浓度差异明显,影响治疗效果和药物不良反应的发生。为了更加科学、规范的检测,判定患者乙酰化类型,并依据乙酰化类型对患者异烟肼用药剂量实施精准指导,针对不同乙酰化类型的判定方法、药物代谢特点、对临床疗效和药物不良反应发生的影响、相应患者异烟肼用药剂量调整原则,以及开展NAT2基因多态性检测的注意事项等重要问题,首都医科大学附属北京胸科医院和《中国防痨杂志》编辑委员会共同组织结核病治疗领域和药理学领域的知名专家,结合现有指南及公开发表的专业文献,经充分讨论,形成本共识。

Expert consensus on polymorphism detection of N-acetyltransferase-2 encoding gene and appropriate isoniazid dosing for tuberculosis patients

Isoniazid (INH) is one of the core drugs in the anti-tuberculosis (anti-TB) treatment regimens, and its catabolic speed is dependent on the activity of N-acetyltransferase-2 (NAT2). According to polymorphisms of the enzyme encoding gene NAT2, patients could be categorized as slow, intermediate or fast acetylators. The significant blood concentration difference was found in the deployment of uniform INH dosage for different TB patients, it could influence the treatment outcome and the occurrence of adverse drug reactions. To promote more scientific and canonical NAT2 gene polymorphism detection and acetylator type judgement, and then guide the appropriate isoniazid dosing for tuberculosis patients, experts in the field of tuberculosis treatment and pharmacology organized by Beijing Chest Hospital and the Editorial Board of Chinese Anti-tuberculosis Journal composed a consensus with the existing guidelines and published professional literature. This consensus includes the method of acetylator type categorization, the pharmacokinetic features, the influences on treatment outcome and adverse drug reactions, the dose adjustment principle of isoniazid for different acetylator types, and the important concerns on NAT2 polymorphism detection.