Inhaled drug delivery is a promising approach to achieving high lung drug concentrations to facilitate efficient treatment of tuberculosis (TB) and to reduce the overall duration of treatment. Rifampicin is a good candidate for delivery via the pulmonary route. There have been no clinical studies yet at relevant inhaled doses despite the numerous studies investigating its formulation and preclinical properties for pulmonary delivery. This review discusses the clinical implications of pulmonary drug delivery in TB treatment, the drug delivery systems reported for pulmonary delivery of rifampicin, animal models, and the animal studies on inhaled rifampicin formulations, and the research gaps hindering the transition from preclinical development to clinical investigation. A review of reports in the literature suggested there have been minimal attempts to test inhaled formulations of rifampicin in laboratory animals at relevant high doses and there is a lack of appropriate studies in animal models. Published studies have reported testing only low doses (≤ 20 mg/kg) of rifampicin, and none of the studies has investigated the safety of inhaled rifampicin after repeated administration. Preclinical evaluations of inhaled anti-TB drugs, such as rifampicin, should include high-dose formulations in preclinical models, determined based on allometric conversions, for relevant high-dose anti-TB therapy in humans.

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吸入利福平临床转化的制剂和临床前研究综述

吸入药物输送是一种有前途的方法，可实现高肺部药物浓度，以促进结核病 (TB) 的有效治疗并缩短治疗的总持续时间。利福平是通过肺部途径递送的良好候选者。尽管有大量研究调查了其肺部给药的配方和临床前特性，但还没有相关吸入剂量的临床研究。这篇综述讨论了肺部给药在结核病治疗中的临床意义、报道的利福平肺部给药系统、动物模型和吸入利福平制剂的动物研究，以及阻碍从临床前开发向临床研究过渡的研究差距. 对文献报告的回顾表明，很少有人尝试在实验室动物中测试相关高剂量的利福平吸入制剂，并且缺乏对动物模型的适当研究。已发表的研究报告仅测试了低剂量 (≤ 20 mg/kg) 的利福平，并且没有一项研究调查重复给药后吸入利福平的安全性。吸入性抗结核药物（如利福平）的临床前评估应包括临床前模型中的高剂量制剂，根据异速生长转化确定，用于人类相关的高剂量抗结核治疗。已发表的研究报告仅测试了低剂量 (≤ 20 mg/kg) 的利福平，并且没有一项研究调查重复给药后吸入利福平的安全性。吸入性抗结核药物（如利福平）的临床前评估应包括临床前模型中的高剂量制剂，根据异速生长转化确定，用于人类相关的高剂量抗结核治疗。已发表的研究报告仅测试了低剂量 (≤ 20 mg/kg) 的利福平，并且没有一项研究调查重复给药后吸入利福平的安全性。吸入性抗结核药物（如利福平）的临床前评估应包括临床前模型中的高剂量制剂，根据异速生长转化确定，用于人类相关的高剂量抗结核治疗。

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