Prospects of Inhalable Formulations of Conventionally Administered Repurposed Drugs for Adjunctive Treatment of Drug-Resistant Tuberculosis: Supporting Evidence from Clinical Trials and Cohort Studies.

IF 2 4区 医学 Q3 RESPIRATORY SYSTEM
Rajeev Ranjan, Venkata Siva Reddy Devireddy
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引用次数: 0

Abstract

Background: Drug resistant tuberculosis is a major public health concern, since the causative agent Mycobacterium tuberculosis is resistant to the most effective drugs against tuberculosis treatment ie., rifampicin and isoniazid. Globally, it accounts 4.6 percent of the patients with tuberculosis, but in some low socioeconomic areas this proportion exceeds to 25 percent. The treatment of drug resistant tuberculosis is prolonged (9-12 months) and often have less favorable outcome with novel as well as recently repurposed drugs administered by conventional routes. Materials and Methods: Clinically, these repurposed drugs have shown several major concerns including low penetration of the drugs to the pulmonary region, emergence of resistant forms, first pass effects, drug-drug interactions, food effects, and serious side effects upon administration by conventional route of administration. Although, several antimicrobial agents have been either approved or are under investigation at different stages of clinical trials and in pre-clinical studies via inhalation route for the treatment of respiratory infections, inhalable formulation for the treatment of drug resistant tuberculosis is most untouched aspect of drug delivery to validate clinically. Only a single dry powder inhalation formulation of capreomycin is able to reach the milestone, ie., phase I for the treatment of drug resistant tuberculosis. Results: Administering inhalable formulations of repurposed drugs as adjuvant in the treatment of drug resistant tuberculosis could mitigate several concerns by targeting drugs directly in the vicinity of bacilli. Conclusion: This review focuses on the limitations and major concerns observed during clinical trials of repurposed drugs (host directed or bactericidal drugs) administered conventionally for the treatment of drug resistant tuberculosis. The outcomes and the concerns of these clinical trials rationalized the need of repurposing formulation which could be administered by inhalation route as adjunctive treatment of drug resistant tuberculosis. [Figure: see text].

背景:耐药性结核病是一个重大的公共卫生问题,因为结核分枝杆菌对治疗结核病的最有效药物(利福平和异烟肼)具有耐药性。在全球范围内,耐药性结核病患者占结核病患者总数的 4.6%,但在一些社会经济水平较低的地区,这一比例超过了 25%。耐药性肺结核的治疗时间较长(9-12 个月),通过常规途径使用新型药物和最近重新设计的药物,疗效往往较差。材料与方法:在临床上,这些再利用药物显示出几个主要问题,包括药物在肺部的低渗透性、耐药形式的出现、首过效应、药物间相互作用、食物效应以及通过常规途径给药时产生的严重副作用。虽然有几种抗菌剂已经获得批准,或正在不同阶段的临床试验和临床前研究中调查通过吸入途径治疗呼吸道感染的情况,但用于治疗耐药性结核病的吸入制剂是最有待临床验证的给药方式。只有一种卡曲霉素干粉吸入制剂能够达到治疗耐药性结核病的里程碑,即 I 期治疗。结果在治疗耐药性结核病的过程中,作为辅助药物使用的可吸入制剂可将药物直接作用于结核杆菌附近,从而缓解了一些问题。结论:本综述重点讨论了在以传统方法治疗耐药性结核病的再利用药物(针对宿主或杀菌药物)临床试验中观察到的局限性和主要问题。这些临床试验的结果和关注点使人们认识到,有必要重新设计可通过吸入途径给药的制剂,以辅助治疗耐药性结核病。[图:见正文]。
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来源期刊
CiteScore
6.70
自引率
2.90%
发文量
34
审稿时长
>12 weeks
期刊介绍: Journal of Aerosol Medicine and Pulmonary Drug Delivery is the only peer-reviewed journal delivering innovative, authoritative coverage of the health effects of inhaled aerosols and delivery of drugs through the pulmonary system. The Journal is a forum for leading experts, addressing novel topics such as aerosolized chemotherapy, aerosolized vaccines, methods to determine toxicities, and delivery of aerosolized drugs in the intubated patient. Journal of Aerosol Medicine and Pulmonary Drug Delivery coverage includes: Pulmonary drug delivery Airway reactivity and asthma treatment Inhalation of particles and gases in the respiratory tract Toxic effects of inhaled agents Aerosols as tools for studying basic physiologic phenomena.
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