气道疾病对吸入药物沉积的影响。

Expert opinion on drug delivery Pub Date : 2024-08-01 Epub Date: 2024-08-19 DOI:10.1080/17425247.2024.2392790
Chantal Darquenne, Timothy E Corcoran, Federico Lavorini, Alessandra Sorano, Omar S Usmani
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摘要

简介吸入药物的沉积是肺部药代动力学过程中产生治疗反应的第一步。不仅是肺部剂量,更重要的是沉积药物在肺部不同区域的分布决定了局部生物利用度、疗效和临床安全性。对气溶胶沉积模式的评估一直是物理学、放射学、生理学和生物学等领域深入研究的重点:该综述涵盖了气溶胶在肺部传输的物理学原理,确定肺部剂量和气溶胶沉积模式的实验和室内建模方法,哮喘、慢性阻塞性肺病和囊性纤维化对气溶胶沉积的影响,以及确定气溶胶沉积剂量的临床转化潜力:尽管主要是在健康领域,但近来在室内建模和肺部成像方面取得的进展使得针对特定对象的真实气溶胶沉积模型得以开发。肺部疾病的精确建模仍需要进一步完善现有的成像和建模方法,以更好地描述外周气道的疾病异质性。尽管如此,最近在吸入器设备工程方面以患者为中心的创新以及数字技术的融入,已使肺部沉积更加一致,并改善了远端气道的靶向性,从而更好地满足了患者的临床需求。
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The effects of airway disease on the deposition of inhaled drugs.

Introduction: The deposition of inhaled medications is the first step in the pulmonary pharmacokinetic process to produce a therapeutic response. Not only lung dose but more importantly the distribution of deposited drug in the different regions of the lung determines local bioavailability, efficacy, and clinical safety. Assessing aerosol deposition patterns has been the focus of intense research that combines the fields of physics, radiology, physiology, and biology.

Areas covered: The review covers the physics of aerosol transport in the lung, experimental, and in-silico modeling approaches to determine lung dose and aerosol deposition patterns, the effect of asthma, chronic obstructive pulmonary disease, and cystic fibrosis on aerosol deposition, and the clinical translation potential of determining aerosol deposition dose.

Expert opinion: Recent advances in in-silico modeling and lung imaging have enabled the development of realistic subject-specific aerosol deposition models, albeit mainly in health. Accurate modeling of lung disease still requires additional refinements in existing imaging and modeling approaches to better characterize disease heterogeneity in peripheral airways. Nevertheless, recent patient-centric innovation in inhaler device engineering and the incorporation of digital technology have led to more consistent lung deposition and improved targeting of the distal airways, which better serve the clinical needs of patients.

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