Inhaled Delivery of Clofazimine - A High Efficiency, Flow Independent, Targeted, Low Cost DPI

氯法齐明的吸入给药 - 一种高效、不依赖流量、有针对性、低成本的 DPI

• 批准号: 10229327
• 负责人: JOHN KOLENG
• 金额: $ 299.92万
• 依托单位: VIA THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2023-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10229327
• 关键词: Adverse event; Alveolar Macrophages; Animals; Bangladesh; Bypass; Cavia; Development; Drug resistance; Effectiveness; Formulation; Goals; Hand; Inhalation; Inhalators; Leprosy; Lung; Multi-Drug Resistance; Oral; Pharmaceutical Preparations; Population; Powder dose form; Regimen; Reproducibility; Research Priority; Resistance; Safety; System; Tissues; Toxic effect; Tuberculosis; cost; cost efficient; improved; skin discoloration; treatment duration; tuberculosis drugs; tuberculosis treatment

Inhaled Delivery of Clofazimine (CFZ) – An Important Anti-tuberculosis Drug: Development of improved drug regimens to shorten treatment for multidrug-resistant (MDR) and drug susceptible (DS) tuberculosis (TB) and improve tolerance and safety is an extremely high research priority. Clofazimine is a drug approved decades ago for treatment of leprosy. Animal studies of the drug for TB treatment indicate that it may significantly reduce treatment duration, particularly in combinations including PZA. The effectiveness of the “Bangladesh” regimen provides support that inclusion of CFZ in MDR regimens may shorten treatment from 18 to 9-10 months, at least in populations with a low rate of resistance to other MDR drugs. However, tolerance to orally administered clofazimine is often limited by skin discoloration and GI adverse events. In addition, CFZ substantially increased the QT interval. Inhaled delivery offers the potential to bypass these barriers while still maintaining effectiveness in the lungs by achieving high drug concentrations in the infected pulmonary tissue with lower systemic exposure, thus allowing increased immediate potency. The goal is to develop an inexpensive, easy-to-use, inhaled delivery system for clofazimine to be used with combinations of systemic anti-tubercular drugs to improve the treatment of MDR and DS TB.

一种重要的抗结核药物--氯法齐明(CFZ)的吸入给药：开发改进的药物方案，以缩短多药耐药(MDR)和药物敏感(DS)结核病的治疗时间，并提高耐受性和安全性是一项极高的研究重点。氯法齐明是一种几十年前被批准用于治疗麻风的药物。这种治疗结核病的药物的动物研究表明，它可能会显著缩短治疗持续时间，特别是在包括PZA在内的联合治疗中。“孟加拉国”方案的有效性支持了将CFZ纳入MDR方案可能将疗程从18个月缩短到9-10个月，至少在对其他MDR药物耐药率较低的人群中是这样。然而，对口服氯法齐明的耐受性往往受到皮肤变色和胃肠道不良事件的限制。此外，CFZ显著延长了QT间期。吸入给药提供了绕过这些障碍的可能性，同时通过在感染的肺组织中实现较高的药物浓度和较低的全身暴露，仍然保持在肺部的有效性，从而提高了即时效力。其目标是开发一种廉价、易于使用的吸入型氯法齐明给药系统，与全身抗结核药物组合使用，以改善MDR和DS TB的治疗。