PREDICTION OF DRUG RESIDENCE TIMES IN REGIONS OF THE HUMAN RESPIRATORY-TRACT FOLLOWING AEROSOL INHALATION
PREDICTION OF DRUG RESIDENCE TIMES IN REGIONS OF THE HUMAN RESPIRATORY-TRACT FOLLOWING AEROSOL INHALATION
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DOI：
10.1002/jps.2600750502
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发表时间：
1986-05-01
影响因子：
3.8
通讯作者：
BYRON, PR
中科院分区：
文献类型：
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作者：
BYRON, PR
建立了一个预测药物在人体呼吸道不同部位的滞留动力学的数学模型。该模型允许不同剂量组分的区域沉积(根据四种流行的呼吸方式，口腔吸入不同颗粒大小)。预测的肺泡沉积取决于吸入和屏气的方式。然而，纤毛呼吸道中的沉积基本上不受屏气的影响，空气动力学直径在5-9微米(缓慢吸气)和3-6微米(快速吸气)之间的最大值。选定的粘液纤毛和吸收速率常数决定了将选定肺部区域的初始沉积耗尽到选定的最小剂量分数(MDF)所需的持续时间(T)。纤毛呼吸道中MDF为0.01的T值取决于气雾剂的大小、吸入方式和溶解速度。在快速溶解溶质的情况下，最大持续时间很短(1-2小时)，并且发生在颗粒大小和吸入方式时，以使在传导呼吸道中的沉积最大化。然而，对于较难溶解的颗粒，由于对肺泡区颗粒的长期研究，同一呼吸道中的T可能接近12小时。每个病例的最佳大小分布和最长持续时间的吸入方式都有很大不同。该模型能够提出关于吸入治疗性气雾剂后局部药物在RT中停留时间延长的可检验假说。
A mathematical model was developed for predicting drug residence kinetics in various regions of the human respiratory tract (RT). The model allows for regional deposition of different dose fractions (following mouth inhalation of various particle sizes according to four popular breathing regimes). Predicted alveolar deposition was dependent on the mode of inhalation and breath-holding. Deposition in the ciliated airways, however, was largely unaffected by breath-holding and was at a maximum for aerodynamic diameters between 5-9 .mu.m (slow inhalation) and 3-6 .mu.m (fast inhalation). Selected mucociliary and absorption rate constants determined the durations (T) taken to deplete the initial deposition in a chosen lung region to a selected minimum dose fraction (MDF). Values of T for a MDF of 0.01 in the ciliated airways were dependent on aerosol size, mode of inhalation, and rate of dissolution. In the case of rapidly dissolving solutes, the maximum duration was short (1-2 h) and occurred at particle sizes and modes of inhalation which maximized deposition in the conducting airways. For less soluble particles, however, T in the same airways could approach 12 h due to a prolonged study of particles from the alveolar regions. The optimal size distribution and the mode of inhalation for maximum duration differed substantially in each case. The model enables formulation of testable hypotheses relating to the extension of local drug residence in the RT following inhalation of therapeutic aerosols.