Precision Medicine Strategies to Improve Isoniazid Therapy in Patients with Tuberculosis.

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Levin Thomas, Arun Prasath Raju, Surulivelrajan Mallayasamy, Mahadev Rao
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引用次数: 0

Abstract

Due to interindividual variability in drug metabolism and pharmacokinetics, traditional isoniazid fixed-dose regimens may lead to suboptimal or toxic isoniazid concentrations in the plasma of patients with tuberculosis, contributing to adverse drug reactions, therapeutic failure, or the development of drug resistance. Achieving precision therapy for isoniazid requires a multifaceted approach that could integrate various clinical and genomic factors to tailor the isoniazid dose to individual patient characteristics. This includes leveraging molecular diagnostics to perform the comprehensive profiling of host pharmacogenomics to determine how it affects isoniazid metabolism, such as its metabolism by N-acetyltransferase 2 (NAT2), and studying drug-resistant mutations in the Mycobacterium tuberculosis genome for enabling targeted therapy selection. Several other molecular signatures identified from the host pharmacogenomics as well as other omics-based approaches such as gut microbiome, epigenomic, proteomic, metabolomic, and lipidomic approaches have provided mechanistic explanations for isoniazid pharmacokinetic variability and/or adverse drug reactions and thereby may facilitate precision therapy of isoniazid, though further validations in larger and diverse populations with tuberculosis are required for clinical applications. Therapeutic drug monitoring and population pharmacokinetic approaches allow for the adjustment of isoniazid dosages based on patient-specific pharmacokinetic profiles, optimizing drug exposure while minimizing toxicity and the risk of resistance. Current evidence has shown that with the integration of the host pharmacogenomics-particularly NAT2 and Mycobacterium tuberculosis genomics data along with isoniazid pharmacokinetic concentrations in the blood and patient factors such as anthropometric measurements, comorbidities, and type and timing of food administered-precision therapy approaches in isoniazid therapy can be tailored to the specific characteristics of both the host and the pathogen for improving tuberculosis treatment outcomes.

Abstract Image

改善结核病患者异烟肼治疗的精准医学策略。
由于药物代谢和药代动力学的个体差异,传统的异烟肼固定剂量疗法可能会导致结核病患者血浆中的异烟肼浓度不达标或产生毒性,从而导致药物不良反应、治疗失败或耐药性的产生。要实现异烟肼的精准治疗,需要采取多方面的方法,综合各种临床和基因组因素,根据患者的个体特征来调整异烟肼的剂量。这包括利用分子诊断技术对宿主药物基因组学进行全面分析,以确定宿主药物基因组学如何影响异烟肼的代谢,如N-乙酰转移酶2(NAT2)对异烟肼的代谢,以及研究结核分枝杆菌基因组中的耐药突变,以实现靶向治疗的选择。从宿主药物基因组学以及肠道微生物组、表观基因组学、蛋白质组学、代谢组学和脂质组学等其他基于全局组学的方法中发现的其他一些分子特征,为异烟肼药代动力学变异和/或药物不良反应提供了机理解释,从而可能促进异烟肼的精准治疗,但临床应用还需要在更大规模和更多样化的结核病人群中进行进一步验证。通过治疗药物监测和群体药代动力学方法,可以根据患者的特定药代动力学特征调整异烟肼剂量,优化药物暴露,同时最大限度地降低毒性和耐药性风险。目前的证据表明,通过整合宿主药物基因组学,特别是 NAT2 和结核分枝杆菌基因组学数据,以及血液中的异烟肼药代动力学浓度和患者因素(如人体测量、合并症、给药食物的类型和时间),可以根据宿主和病原体的具体特征调整异烟肼治疗的精确治疗方法,从而改善结核病的治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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