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呈现处于不同药物研发阶段的新型抗结核药物的化学类别:2010 - 2020年综述

Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010-2020 Review.

作者信息

Angula Klaudia T, Legoabe Lesetja J, Beteck Richard M

机构信息

Centre of Excellence for Pharmaceutical Sciences (Pharmacen), North-West University, Potchefstroom 2520, South Africa.

出版信息

Pharmaceuticals (Basel). 2021 May 13;14(5):461. doi: 10.3390/ph14050461.

Abstract

Tuberculosis (TB), caused by (Mtb), is a curable airborne disease currently treated using a drug regimen consisting of four drugs. Global TB control has been a persistent challenge for many decades due to the emergence of drug-resistant Mtb strains. The duration and complexity of TB treatment are the main issues leading to treatment failures. Other challenges faced by currently deployed TB regimens include drug-drug interactions, miss-matched pharmacokinetics parameters of drugs in a regimen, and lack of activity against slow replicating sub-population. These challenges underpin the continuous search for novel TB drugs and treatment regimens. This review summarizes new TB drugs/drug candidates under development with emphasis on their chemical classes, biological targets, mode of resistance generation, and pharmacokinetic properties. As effective TB treatment requires a combination of drugs, the issue of drug-drug interaction is, therefore, of great concern; herein, we have compiled drug-drug interaction reports, as well as efficacy reports for drug combinations studies involving antitubercular agents in clinical development.

摘要

由结核分枝杆菌(Mtb)引起的结核病(TB)是一种可治愈的空气传播疾病,目前使用由四种药物组成的治疗方案进行治疗。由于耐药Mtb菌株的出现,全球结核病控制几十年来一直是一项持续的挑战。结核病治疗的持续时间和复杂性是导致治疗失败的主要问题。目前采用的结核病治疗方案面临的其他挑战包括药物相互作用、治疗方案中药物的药代动力学参数不匹配以及对缓慢复制亚群缺乏活性。这些挑战促使人们不断寻找新型结核病药物和治疗方案。本综述总结了正在研发的新型结核病药物/候选药物,重点介绍了它们的化学类别、生物学靶点、耐药产生模式和药代动力学特性。由于有效的结核病治疗需要联合用药,因此药物相互作用问题备受关注;在此,我们汇编了药物相互作用报告以及涉及临床开发中抗结核药物的药物组合研究的疗效报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a9a/8152995/dac41fb3aa2a/pharmaceuticals-14-00461-sch001.jpg

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