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异烟肼诱导的肝毒性与宿主N-乙酰转移酶2基因多态性之间的关联

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

作者信息

Yang S, Guo J Q, Yan X F, Tang Shenjie

机构信息

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.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2022 Feb 12;45(2):227-232. doi: 10.3760/cma.j.cn112147-20210610-00413.

Abstract

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 , but higher plasma concentrations can induce hepatotoxicity or death. Factors that can cause fluctuations in blood concentration include INH absorption ( 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 () 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 tuberculosis. Therefore, further clarification of the correlation between the host genotype and its phenotypic polymorphisms, plasma isoniazid concentration and adverse effects can help to improve the efficacy and minimize the adverse effects.

摘要

异烟肼(INH,H)近七十年来一直是治疗药物敏感型结核病(TB)的关键药物。药代动力学(PK)的差异可能会影响异烟肼的吸收。血浆浓度低与治疗效果较差有关, 但血浆浓度较高会导致肝毒性或死亡。可导致血药浓度波动的因素包括异烟肼的吸收(药物-药物或药物-食物相互作用以及其他疾病,如胃肠道问题、糖尿病或结核病)和肝脏代谢异常。N-乙酰转移酶2()基因多态性显著影响异烟肼的血浆浓度。然而,目前缺乏关于异烟肼治疗引起的药物不良反应管理的指南,针对异烟肼不良反应所采取的唯一措施是根据临床经验突然停药或减少异烟肼剂量,但这些措施可能导致结核病产生耐药性。因此,进一步阐明宿主基因型与其表型多态性、血浆异烟肼浓度和不良反应之间的相关性,有助于提高疗效并将不良反应降至最低。

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