Department of Medicine, University of California, San Diego, CA, USA.
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Expert Opin Drug Deliv. 2024 Aug;21(8):1175-1190. doi: 10.1080/17425247.2024.2392790. Epub 2024 Aug 19.
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.
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.
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.
吸入药物的沉积是产生治疗反应的肺部药代动力学过程的第一步。不仅肺部剂量,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。评估气溶胶沉积模式一直是物理学、放射学、生理学和生物学等领域研究的重点。
本文综述了肺部气溶胶传输的物理学、实验和计算模型方法,以确定肺部剂量和气溶胶沉积模式,哮喘、慢性阻塞性肺疾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。
最近在计算模型和肺部成像方面的进展使得能够开发出逼真的、针对个体的气溶胶沉积模型,尽管主要是在健康人群中。对肺部疾病的准确建模仍需要对现有成像和建模方法进行额外的改进,以更好地描述外周气道的疾病异质性。尽管如此,最近在吸入器装置工程方面的以患者为中心的创新以及数字技术的融入导致了更一致的肺部沉积和对远端气道的更好靶向,更好地满足了患者的临床需求。