3M Pharmaceuticals, St. Paul, Minnesota, USA.
J Aerosol Med Pulm Drug Deliv. 2010 Dec;23(6):355-61. doi: 10.1089/jamp.2009.0783. Epub 2010 Jun 24.
The study objective of this pilot study was to determine the lung delivery of HFA-134a-beclomethasone dipropionate (HFA-BDP; QVAR™) and CFC-beclomethasone dipropionate (CFC-BDP; Becloforte™) with and without the add-on spacers, Aerochamber™, and Volumatic™. The smaller particles of HFA-BDP were presumed to produce greater lung deposition using spacers, with and without a delay [i.e., metered dose inhaler (MDI) actuation into the spacer and subsequent inhalation 0 and 2 sec later], compared with the larger particles of CFC-BDP. The study included a comparison of breathhold effects (i.e., 1 and 10-sec breatholds) on lung deposition.
The study was an open-label design and utilized healthy subjects (n = 12 males). Each arm of the study contained three subjects; thus, outcomes were not powered to assess statistical significance. HFA-BDP and CFC-BDP were radiolabeled with technetium-99m and delivered to subjects.
Results showed that the small particle HFA-BDP lung deposition averaged 52% and was not affected by the use of Aerochamber with or without a spacer delay. The oropharyngeal deposition of HFA-BDP was reduced from approximately 28% to 4% with the Aerochamber. Lung deposition with the large particle CFC-BDP was 3-7% and generally decreased with Aerochamber or Volumatic. A 2-sec time delay between actuation and breath plus the spacer reduced lung deposition slightly but reduced oropharygeal deposition substantially (84% down to 3-20%) using the Aerochamber or Volumatic with and without a spacer delay. HFA-BDP lung deposition was dependent on the breathhold. Lung deposition with HFA-BDP was reduced by 16% with a 1-sec versus 10-sec breathhold. The difference was measured in the increased exhaled fraction, confirming that smaller particles need time to deposit and are exhaled if there is a reduced breathhold. The large particle CFC-BDP lung deposition was not affected by breathhold.
The use of Aerochamber or Volumatic spacers with HFA-BDP did not alter lung deposition but it did reduce oropharyngeal deposition. However, HFA-BDP displayed reduced oropharyngeal deposition without a spacer.
本研究的目的是为了确定在使用和不使用附加储雾罐（Aerochamber 和 Volumatic）的情况下，装有 HFA-134a-丙酸倍氯米松（HFA-BDP；QVAR）和装有 CFC-丙酸倍氯米松（CFC-BDP；Becloforte）的定量吸入器（MDI）的肺部输送情况。由于 HFA-BDP 的颗粒较小，因此预计与 CFC-BDP 的较大颗粒相比，使用储雾罐以及（MDI 启动后先将药物喷入储雾罐，随后在 0 秒和 2 秒后吸入药物）可以增加肺部沉积量。该研究还包括对呼吸暂停（即 1 秒和 10 秒呼吸暂停）对肺部沉积的影响进行了比较。
该研究为开放标签设计，纳入了健康受试者（n=12 名男性）。研究的每个部分都包含 3 名受试者，因此，其结果没有足够的效力来评估统计学意义。HFA-BDP 和 CFC-BDP 都用锝-99m 进行放射性标记，然后输送给受试者。
结果表明，小颗粒 HFA-BDP 的肺部沉积平均为 52%，且不受使用装有或不装有储雾罐的 Aerochamber 的影响。使用 Aerchamber 后，HFA-BDP 的咽腔沉积从大约 28%减少到 4%。大颗粒 CFC-BDP 的肺部沉积率为 3-7%，并且通常随着 Aerchamber 或 Volumatic 的使用而降低。在使用装有或不装有储雾罐的 Aerchamber 或 Volumatic 时，在启动和呼吸加上储雾罐之间增加 2 秒的时间延迟，略微降低了肺部沉积率，但显著降低了咽腔沉积率（从 84%降至 3-20%）。HFA-BDP 的肺部沉积率取决于呼吸暂停。与 10 秒呼吸暂停相比，使用 1 秒呼吸暂停会使 HFA-BDP 的肺部沉积率降低 16%。这一差异可以通过呼出分数的增加来测量，这证实了较小的颗粒需要时间沉积，如果呼吸暂停时间较短，就会被呼出。大颗粒 CFC-BDP 的肺部沉积率不受呼吸暂停的影响。
使用装有 HFA-BDP 的 Aerchamber 或 Volumatic 储雾罐并没有改变肺部沉积率，但确实减少了咽腔沉积率。然而，HFA-BDP 即使没有储雾罐也能减少咽腔沉积。
