抗非结核分枝杆菌药物临床前药效学研究模型应用现状与展望

Current status and future prospects of preclinical pharmacodynamic models for anti-non-tuberculous mycobacterial agents

摘要

非结核分枝杆菌肺病（NTM-PD）发病率逐年上升,该类疾病疗程长、联合用药复杂、不良反应发生率高,对新型药物的研发提出紧迫需求。然而非结核分枝杆菌种类繁多、菌种异质性强,传统的临床前药效学研究与临床疗效之间常存在差异。本文围绕抗非结核分枝杆菌药物研发,梳理体外模型、细胞模型和动物模型的应用现状,重点比较各类模型的优缺点,并分析抗NTM模型体系的特殊需求。以期为构建更加合理、高效的抗NTM药物临床前药效评估体系,以及提高候选药物筛选效率和临床转化成功率提供参考。

Abstract

The incidence of non-tuberculous mycobacteria pulmonary disease (NTM-PD) has been rising annually. This disease is characterized by a long treatment duration, complex combination therapy, and a high incidence of adverse reactions, which creates an urgent need for the development of new drugs. Nevertheless, non-tuberculous mycobacteria are diverse and exhibit strong species heterogeneity. There is often a disparity between traditional pre-clinical pharmacodynamics research and clinical efficacy. The author focuses on the research and development of anti-non-tuberculous mycobacteria drugs, summarizes the application status of in vitro models, cell models, and animal models, and comprehensively compares the advantages and disadvantages of various models. The specific requirements of the anti-NTM model system are also analyzed. The objective is to offer a reference for the construction of a more rational and efficient pre-clinical pharmacodynamics evaluation system for anti-NTM drugs, as well as to enhance the efficiency of candidate drug screening and the success rate of clinical conversion.

关键词

非结核分枝杆菌 / 药物研发 / 临床前模型 / 药效学

Key words

nontuberculous mycobacteria / drug development / preclinical models / pharmacodynamic

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基金资助

国家自然科学基金资助项目(82173862)

贵州省卫生健康委临床重点专科“攀峰计划”建设项目(GZWJWPF2025010)

北京市医院管理中心“登峰”人才培养计划(DFL20221402)