Intrapulmonary distribution of deposited particles
Intrapulmonary distribution of deposited particles
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DOI：
10.1089/jam.1999.12.275
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发表时间：
1999-12-01
期刊：
影响因子：
--
通讯作者：
Heyder, J
中科院分区：
文献类型：
--
作者：
Brand, P;H채ussinger, K;Heyder, J
吸入给药无论是局部治疗还是全身治疗，都比口服、静脉或皮下给药有许多优点。由于一些药物应该沉积在支气管树内，其他药物应该沉积在肺的呼吸区内，因此应该有可能确定和影响药物沉积的优先位置，以制定有效的吸入治疗策略。在这篇文章中，介绍了一种方法，该方法可以估计个体受试者肺部沉积颗粒的纵向分布。从单分散的癸二酸二乙基己酯(DEHS)液滴的光度测量中，可以评估沉积颗粒的纵向分布(即，沉积在特定肺体积元素中的颗粒数量)。在这项研究中，在四名健康志愿者身上，评估了不同气流速度、潮气量(V(T)、S)和颗粒大小下沉积颗粒的分布。结果表明，不同受试者沉积颗粒的纵向分布有很大差异，并且这种分布强烈依赖于颗粒尺寸：如果颗粒尺寸增大，颗粒沉积位置将向近端移动。直径大于约5微米的颗粒不能穿透到大于约600厘米(3)的体积肺深度(V-P)，即使增大了V-T。风量对沉积颗粒的分布影响不大，但随着风量的增加，颗粒沉积的位置略有外移。该方法可用于非侵入性地研究人体肺部药物沉积的个体模式，并开发和优化吸入给药策略。
Inhalation drug delivery for both topical and systemic treatments has many advantages over oral, intravenous, or subcutaneous drug delivery. Because some drugs should be deposited within the bronchial tree and others should deposit within the respiratory zone of the lung, it should be possible to determine and influence the preferential site of drug deposition to develop efficient inhalation therapy strategies. In this article, a method that allows estimation of the longitudinal distribution of deposited particles in the lungs of individual subjects is introduced. From the photometrically measured deposition of monodisperse di-2-ethylhexyl sebacate (DEHS) droplets, the longitudinal distribution of deposited particles (i.e., the number of particles that are deposited in a certain lung volume element) can be assessed. In this study in four healthy volunteers the distribution of deposited particles was assessed for different airflow rates, tidal volumes (V(T)s), and particle sizes. The results showed that there are considerable differences in the longitudinal distribution of deposited particles between subjects and that the distribution is strongly dependent on particle size: if particle size is increased, the site of particle deposition is shifted proximally. Particles with diameters greater than approximately 5 mu m cannot penetrate to a volumetric lung depth (V-p) greater than approximately 600 cm(3) even if the V-T is increased. Airflow rate has a minor effect on the distribution of deposited particles, but if airflow rate increases, the site of particle deposition is slightly shifted peripherally. This method can be used to investigate individual patterns of drug deposition in human lungs noninvasively and to develop and optimize inhalation strategies for inhalation drug delivery.