Katz Sherri L, Adatia Ian, Louca Emily, Leung Kitty, Humpl T, Reyes Janette T, Coates Allan L
Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
Pediatr Pulmonol. 2006 Jul;41(7):666-73. doi: 10.1002/ppul.20431.
Sildenafil, tezosentan, and prostacyclin reduce pulmonary vascular pressures in pulmonary hypertension, but have potential to vasodilate the systemic circulation. Nebulized vasodilators allow targeted drug delivery, high local drug concentrations, less systemic hypotension, and better matching of the lung's ventilation and perfusion. We aimed to estimate pulmonary deposition of these drugs from commonly employed nebulizers using in vitro techniques and to create a mathematical model to predict inspired mass of aerosol.
Lung deposition was estimated by characterization of drug output and particle size distribution (PSD) of nebulizers using helium-neon laser diffraction techniques. A mathematical model for each device was created to estimate pulmonary deposition using patients' breathing patterns and was verified with a mechanical-breathing model.
Total output and PSD were similar for the Hudson Updraft II and Whisperjet nebulizers, consisting of half the nebulizer's charge, with (1/4) of particles < or = 5 microm, in the respirable fraction (RF). Drug output increased with inspiratory flow for the Pari LC Star. Differences were noted in device performance, depending on the drug tested. Estimated pulmonary deposition (mean, 95% CI) was 8.1 (7.2, 9.0)% of the initial drug charge for the Hudson Updraft II, 6.4 (5.8, 7.0)% for the Whisperjet, and 33.0 (28.3, 37.9)% for the Pari LC Star. A mechanical model was consistent with our mathematical model.
All drugs could be nebulized, but expected pulmonary deposition varied depending on the nebulizer and drug.
西地那非、替唑生坦和前列环素可降低肺动脉高压患者的肺血管压力，但有可能导致体循环血管舒张。雾化血管扩张剂可实现靶向给药、提高局部药物浓度、减少全身性低血压，并更好地匹配肺的通气和灌注。我们旨在使用体外技术估算这些药物在常用雾化器中的肺部沉积量，并创建一个数学模型来预测吸入气雾剂的质量。
通过使用氦氖激光衍射技术对雾化器的药物输出和粒径分布（PSD）进行表征，来估算肺部沉积量。针对每个设备创建了一个数学模型，以利用患者的呼吸模式估算肺部沉积量，并通过机械呼吸模型进行验证。
Hudson Updraft II雾化器和Whisperjet雾化器的总输出量和PSD相似，在可吸入部分（RF）中，由雾化器一半的药量组成，其中（1/4）的颗粒直径≤5微米。Pari LC Star雾化器的药物输出量随吸气流量增加。根据所测试的药物，各设备的性能存在差异。Hudson Updraft II雾化器的估计肺部沉积量（平均值，95%置信区间）为初始药量的8.1%（7.2%，9.0%），Whisperjet雾化器为6.4%（5.8%，7.0%），Pari LC Star雾化器为33.0%（28.3%，37.9%）。一个机械模型与我们的数学模型一致。
所有药物均可雾化，但预期的肺部沉积量因雾化器和药物而异。
