Lipworth B J, Clark D J
Department of Clinical Pharmacology, Ninewalls Hospital and Medical School, University of Dundee.
Br J Clin Pharmacol. 1998 Jul;46(1):45-8. doi: 10.1046/j.1365-2125.1998.00041.x.
To evaluate the lung dose of a non-CFC salbutamol metered dose inhaler (MDI) formulation via three commonly used plastic spacer devices, of both large and small volume, compared with the MDI used on its own.
Ten healthy volunteers were studied in a randomized single (investigator) blind crossover design. Single 1200 microg nominal doses of salbutamol from a non-CFC MDI (Airomir), as 12 sequential 100 microg puffs over 6 min, were delivered from the MDI alone and via two large volume spacer devices (Nebuhaler, Volumatic), and a small volume spacer (Aerochamber). All spacers were prewashed prior to each study day and mouth rinsing was performed after each drug sequence. Plasma salbutamol was measured at 5, 10, 15 and 20 min, with calculation of maximum (Cmax) and average (Cav) concentrations. This lung dose was assessed using the early lung absorption profile of salbutamol in the first 20 min after inhalation.
Both of the large volume spacers, the Nebuhaler and the Volumatic, delivered significantly more salbutamol than the MDI alone. For Cav this amounted to a 2.07-fold difference (95% CI 1.48-2.90) between Nebuhaler vs MDI, and a 1.49-fold difference (95%CI 1.19-1.87) between Volumatic vs MDI. The Nebuhaler also produced greater deposition than either the Volumatic or the Aerochamber spacers; Nebuhaler vs Volumatic: 1.39-fold difference (95% CI 1.09-1.76), Nebuhaler vs Aerochamber: 1.63-fold difference (95% CI 1.20-2.21). There were no significant differences between the Aerochamber and the MDI alone.
Using the early lung absorption profile, for administration of the same nominal dose, both of the large volume spacers (Nebuhaler and Volumatic) but not the small volume spacer (Aerochamber) delivered significantly more salbutamol than the MDI alone. The Nebuhaler also produced greater delivery than either the Volumatic or the Aerochamber spacer devices. Our results show that whilst lung delivery of non-CFC salbutamol MDI is improved by the use of a plastic spacer, there may be appreciable differences in performance, particularly between large and small volume devices.
通过三种常用的大小不同的塑料储雾罐装置，评估不含氯氟烃的沙丁胺醇定量气雾剂（MDI）制剂的肺部剂量，并与单独使用MDI进行比较。
采用随机单（研究者）盲交叉设计对10名健康志愿者进行研究。从不含氯氟烃的MDI（Airomir）中单次给予1200微克标称剂量的沙丁胺醇，在6分钟内分12次依次喷出，每次100微克，分别通过单独的MDI以及两个大容量储雾罐装置（Nebuhaler、Volumatic）和一个小容量储雾罐（Aerochamber）给药。在每个研究日之前，所有储雾罐均预先清洗，并且在每个药物给药序列后进行漱口。在5、10、15和20分钟时测量血浆沙丁胺醇，计算最大（Cmax）和平均（Cav）浓度。使用吸入后最初20分钟内沙丁胺醇的早期肺部吸收情况评估肺部剂量。
两个大容量储雾罐Nebuhaler和Volumatic输送的沙丁胺醇均明显多于单独使用MDI。对于Cav，Nebuhaler与MDI之间的差异为2.07倍（95%CI 1.48 - 2.90），Volumatic与MDI之间的差异为1.49倍（95%CI 1.19 - 1.87）。Nebuhaler产生的沉积也比Volumatic或Aerochamber储雾罐更多；Nebuhaler与Volumatic相比：差异为1.39倍（95%CI 1.09 - 1.76），Nebuhaler与Aerochamber相比：差异为1.63倍（95%CI 1.20 - 2.21）。Aerochamber与单独使用MDI之间无显著差异。
利用早期肺部吸收情况，对于相同的标称剂量给药，两个大容量储雾罐（Nebuhaler和Volumatic）而非小容量储雾罐（Aerochamber）输送的沙丁胺醇明显多于单独使用MDI。Nebuhaler产生的输送量也比Volumatic或Aerochamber储雾罐装置更多。我们的结果表明，虽然使用塑料储雾罐可改善不含氯氟烃的沙丁胺醇MDI的肺部给药，但在性能上可能存在明显差异，尤其是在大容量和小容量装置之间。
