Lipworth B J, Clark D J
Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital & Medical School, University of Dundee.
Br J Clin Pharmacol. 1998 Feb;45(2):160-3. doi: 10.1046/j.1365-2125.1998.00648.x.
To compare the lung delivery of salbutamol from a commonly used constant output open vent jet nebuliser (Sidestream) with use of both a conventional large volume plastic spacer (Volumatic) and a novel small volume metal spacer (NebuChamber). This was assessed using the early lung absorption profile of salbutamol over the first 20 min after inhalation.
Twelve healthy volunteers were studied in a randomized single (investigator) blind crossover design. Single 1200 microg nominal doses salbutamol from a CFC-free metered-dose inhaler (12 sequential 100 microg puffs of Airomir) were delivered via the Volumatic and NebuChamber spacers. A single 1200 microg nominal dose of salbutamol was given as a 4 ml fill volume from a Sidestream nebuliser with mouthpiece. Mouth rinsing was performed after each drug sequence. Plasma salbutamol was measured at 5, 10, 15 and 20 min after the last dose of each inhalation sequence, with calculation of maximal concentration (Cmax) and average concentration over 20 min (C[av]). Systemic beta2-responses were measured as plasma potassium, tremor and heart rate.
Both the Volumatic and the NebuChamber spacers produced significantly greater salbutamol concentration than the Sidestream nebuliser. For C(av) this amounted to a 7.34-fold difference (95%CI 5.31 to 9.38) between Volumatic vs Sidestream, and a 7.04-fold difference (95%CI 4.91 to 9.17) for NebuChamber vs Sidestream. Similar differences were found for the extrapulmonary beta2-responses. There were no significant differences in either salbutamol concentration or extrapulmonary beta2-responses between the Volumatic and NebuChamber spacers.
We found that, in vivo, both the Volumatic and the NebuChamber spacers produced seven-fold greater lung delivery of salbutamol than the Sidestream nebuliser when comparing microgram equivalent nominal doses, in terms of the early lung absorption profile.
比较使用传统大容量塑料储雾罐（Volumatic）和新型小容量金属储雾罐（NebuChamber）时，常用的恒量输出开放式喷射雾化器（旁流式）吸入沙丁胺醇后在肺内的递送情况。通过吸入后最初20分钟内沙丁胺醇的早期肺吸收情况进行评估。
采用随机单（研究者）盲交叉设计对12名健康志愿者进行研究。通过Volumatic和NebuChamber储雾罐递送来自不含氟氯化碳的定量吸入器（12次连续100微克的Airomir喷雾）的单次1200微克标称剂量沙丁胺醇。使用带咬嘴的旁流式雾化器以4毫升填充量给予单次1200微克标称剂量的沙丁胺醇。每个药物给药顺序后进行漱口。在每次吸入顺序的最后一剂后5、10、15和20分钟测量血浆沙丁胺醇，计算最大浓度（Cmax）和20分钟内的平均浓度（C[av]）。将全身β2反应测量为血浆钾、震颤和心率。
Volumatic和NebuChamber储雾罐产生的沙丁胺醇浓度均显著高于旁流式雾化器。对于C（av），Volumatic与旁流式雾化器之间的差异为7.34倍（95%CI 5.31至9.38），NebuChamber与旁流式雾化器之间的差异为7.04倍（95%CI 4.91至9.17）。在肺外β2反应方面也发现了类似差异。Volumatic和NebuChamber储雾罐在沙丁胺醇浓度或肺外β2反应方面均无显著差异。
我们发现，在体内，就早期肺吸收情况而言，当比较微克当量标称剂量时，Volumatic和NebuChamber储雾罐吸入沙丁胺醇后在肺内的递送量均比旁流式雾化器高7倍。
