Ito Kazuhiro
Respiratory Molecular Medicine, Genomic and Environmental Medicine section, National Heart and Lung Institute, Imperial College, London, UK.
Expert Opin Drug Deliv. 2022 Jul;19(7):755-769. doi: 10.1080/17425247.2022.2084530. Epub 2022 Jun 2.
Disease due to pulmonary infection with , and other emerging opportunistic fungi remains a significant unmet need. Existing antifungal medicines are predominantly dosed either orally or systemically, but because of limited exposure to the lung lumen, adverse events, and problematic drug-drug interactions, inhaled treatment could provide an attractive option.
This review summarizes 1) the limitations of current antifungal therapy, 2) the beneficial effects of inhaled antifungal agents, 3) the clinical development of inhaled antifungal triazoles (repurposed with an innovative inhalation system or a novel inhaled agent) for the treatment of pulmonary fungal infections, and 4) the difficulties and challenges of inhaled antifungal agent development. Regrettably, details of novel inhaled devices or formulations were not covered.
Inhaled antifungal treatment could provide an attractive option by shifting the risk benefit ratio of treatment favorably. Preclinical and clinical studies with inhaled antifungal agents (off-label use) are encouraging so far. New inhaled antifungal triazoles are well tolerated in early clinical studies and warrant further clinical development. However, challenges remain and many unaddressed issues including required preclinical studies, appropriate clinical design, pharmacokinetics, delivery system(s) and regulatory process need to be resolved. Early communication with regulatory authorities is therefore recommended.
由烟曲霉及其他新出现的机会性真菌引起的肺部感染疾病，仍然是一个尚未得到充分满足的重大需求。现有的抗真菌药物主要通过口服或全身给药，但由于肺部管腔暴露有限、不良事件以及药物相互作用问题，吸入治疗可能是一个有吸引力的选择。
本综述总结了：1）当前抗真菌治疗的局限性；2）吸入性抗真菌药物的有益效果；3）吸入性抗真菌三唑类药物（通过创新吸入系统或新型吸入剂重新利用）治疗肺部真菌感染的临床进展；4）吸入性抗真菌药物研发的困难与挑战。遗憾的是，未涵盖新型吸入装置或制剂的详细信息。
吸入性抗真菌治疗通过有利地改变治疗的风险效益比，可能提供一个有吸引力的选择。到目前为止，吸入性抗真菌药物的临床前和临床研究（标签外使用）令人鼓舞。新型吸入性抗真菌三唑类药物在早期临床研究中耐受性良好，值得进一步开展临床研究。然而，挑战依然存在，许多问题尚未解决，包括所需的临床前研究、合适的临床设计、药代动力学、给药系统和监管程序等，都需要解决。因此，建议尽早与监管机构沟通。
