Madney Yasmin M, Harb Hadeer S, Porée Thierry, Eckes Myriam, Boules Marina E, Abdelrahim Mohamed E A
Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-suef, Egypt.
ProtecSom-OptimHal, Valognes, France.
Exp Lung Res. 2022 Mar 2:1-9. doi: 10.1080/01902148.2022.2047243.
This study aimed to evaluate the effect of a preliminary bronchodilator dose on the aerosol-d elivery by different nebulizers in noninvasively ventilated chronic obstructive pulmonary disease (COPD) patients. COPD patients were randomized to receive study doses of 800 µg beclomethasone dipropionate (BPD) nebulized by either a vibrating mesh nebulizer (VMN) or a jet nebulizer (JN) connected to MinimHal spacer device. On a different day, the nebulized dose of beclomethasone was given to each patient by the same aerosol generator with and without preceded two puffs (100 µg each) of salbutamol delivered by a pressurized-metered dose inhaler. Urinary BPD and its metabolites in 30 min post-inhalation samples and pooled up to 24 h post-inhalation were measured. On day 2, ex-vivo studies were performed with BPD collected on filters before reaching patients which were eluted from filters and analyzed to estimate the total emitted dose. The highest urinary excretion amounts of BPD and its metabolites 30 min and 24 h post-inhalation were identified with pMDI + VMN compared with other regimens( < 0.001). The amounts of BPD and its metabolites excreted 30 min post inhalation had approximately doubled with pMDI + JN compared with JN delivery ( < 0.05). No significant effect was found in the ex-vivo study results except between VMN and JN with a significant superiority of the VMN ( < 0.001). Using a preliminary bronchodilator dose before drug nebulization significantly increased the effective lung dose of the nebulized drug with both VMNs and JNs. However, adding a preliminary bronchodilator dose increased the 24 hr cumulative urinary amount of the drug representing higher systemic delivery of the drug, which in turn could result in higher systemic side effects.
本研究旨在评估初始支气管扩张剂剂量对不同雾化器在无创通气的慢性阻塞性肺疾病（COPD）患者中气溶胶递送的影响。COPD患者被随机分为两组，分别接受通过振动网式雾化器（VMN）或与MinimHal储雾罐装置相连的喷射雾化器（JN）雾化的800µg丙酸倍氯米松（BPD）研究剂量。在另一天，由同一气溶胶发生器对每位患者进行丙酸倍氯米松雾化给药，给药前分别给予或不给予通过压力定量吸入器递送的两喷（每次100µg）沙丁胺醇。测量吸入后30分钟及合并至吸入后24小时的尿液中BPD及其代谢物含量。在第2天，对在到达患者之前收集在滤器上的BPD进行离体研究，将其从滤器上洗脱并分析以估计总释放剂量。与其他给药方案相比，吸入后30分钟和24小时，使用压力定量吸入器联合VMN时BPD及其代谢物的尿排泄量最高（<0.0）。与JN给药相比，吸入后30分钟，使用压力定量吸入器联合JN时BPD及其代谢物的排泄量增加了约一倍（<0.05）。离体研究结果中未发现显著影响，但VMN和JN之间存在显著差异，VMN具有显著优势（<0.001）。在药物雾化前使用初始支气管扩张剂剂量可显著增加VMN和JN雾化药物的有效肺剂量。然而，添加初始支气管扩张剂剂量会增加药物的24小时累积尿排泄量，这代表药物的全身递送增加，进而可能导致更高的全身副作用。
