In vivo measurements of aerosol dose and distribution: Clinical relevance
In vivo measurements of aerosol dose and distribution: Clinical relevance
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DOI：
10.1089/jam.1996.9.suppl_1.s-77
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Laube, BL
中科院分区：
文献类型：
--
作者：
Laube, BL
数学和体外模型，包括颗粒直径、正常呼吸频率和潮气量，已经被用来预测可呼吸气溶胶在肺部的沉积比例。尽管在药物开发中非常有用，但仅基于这种模型的剂量和剂量分布的确定可能不如活体测量准确，活体测量是在综合了决定气溶胶沉积的所有因素的影响的条件下进行的，包括疾病的影响。伽玛射线照相提供了一种体内量化总沉积分数和下呼吸道内剂量分布的方法。使用这项技术，已经表明下呼吸道的沉积分数可能在MDI或雾化器驱动的剂量的1-30%之间变化。这种储存剂量的大范围表明，临床上对吸入气雾剂的反应的差异可以通过给药剂量的变化来解释，特别是如果雾化药物的治疗范围很窄。吸入药物在肺内分布的变化也可能影响临床反应，因此，某些疾病可能最好通过将药物靶向于肺的特定位置来治疗，而另一些疾病可能对雾化药物的均匀分布产生最佳反应。体内测量将提供对沉积剂量和分布模式的确认，这应该会改善大多数雾化药物的治疗结果。
Mathematical and in vitro models, that incorporate particle diameter, normal breathing frequencies and tidal volumes, have been used to predict the deposition fraction of respirable aerosols within the lungs. Although very useful in drug development, determinations of dose and the distribution of dose based solely on such models may be less accurate than in vivo measurements, which are performed under conditions that combine the effects of all the factors that determine aerosol deposition, including the effect of disease. Gammascintigraphy provides a method for in vivo quantification of the total deposited fraction and the distribution of the dose within the lower respiratory tract. Using this technology, it has been shown that deposition fraction in the lower respiratory tract may vary between 1-30% of the dose actuated from an MDI or nebulizer. This wide range in deposited dose suggests that variations in the clinical response to inhaled aerosols may be explained by alterations in the dose delivered, especially if the aerosolized medication has a narrow therapeutic range. Alterations in the distribution of inhaled drugs within the lungs may also affect the clinical response, such that some disorders may best be treated by targeting drug to specific locations of the lung, while others may respond best to homogeneous distribution of aerosolized drug. In vivo measurements would provide confirmation of the dose deposited as well as the pattern of distribution, which should improve the therapeutic outcome of most aerosolized medications.