Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone
Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone
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DOI：
10.1183/09031936.98.12061346
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发表时间：
1998-12-01
影响因子：
24.3
通讯作者：
Boudreau, RJ
中科院分区：
文献类型：
--
作者：
Leach, CL;Davidson, PJ;Boudreau, RJ
氢氟烷烃-134a（HFA）二丙酸倍氯米松（BDP）被配制成定量吸入器（MDI），以递送1，1 μ m的粒度，而目前标记的氯氟烃（CFC）-BDP产品的粒度为3.5 μ m。在没有附加间隔器的按压-呼吸致动器中使用锝99 m-放射性标记的BDP进行了两项I期单剂量人体沉积研究。一项健康志愿者研究（n=6）显示，55-60%的HFA-BDP在致动器外的剂量沉积在肺部，29-30%沉积在口咽部。CFC-BDP沉积在肺中为4-7%，在口咽中为90-94%。肺内的沉积模式显示，HFA-BDP在整个肺气道中弥漫扩散，而CFC-BDP仅限于中央气道，几乎没有（如果有的话）外周气道沉积。另一项针对哮喘患者的研究（n=16）证实，56%的HFA-BDP剂量沉积在气道中，33%沉积在口咽部。总之，氢氟烷-134 α-二丙酸倍氯米松在气道中的沉积比氯氟烃-二丙酸倍氯米松大得多，同时口咽部沉积减少。氢氟烷推进剂的肺沉积效率增加，导致达到类似疗效所需的二丙酸倍地米松量减少。氢氟烷烃渗透到小气道可以提供常规氯氟烃所不能提供的哮喘治疗。
Hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) was formulated in a metered-dose inhaler (MDI) to deliver a particle size of I,I pm compared with 3.5 microns for currently marked chlorofluorocarbon (CFC)-BDP products. Two phase I single-dose human deposition studies were conducted using technetium 99m-radiolabelled BDP in a press-and-breathe actuator without an add-on spacer.A healthy volunteer study (n=6) showed that 55-60% of the HFA-BDP ex-actuator dose was deposited in the lungs, with 29-30% deposited in the oropharynx.. CFC-BDP deposition was 4-7% in the lungs and 90-94% in the oropharynx. The pattern of deposition within the lung showed that HFA-BDP was spread diffusely throughout the lung airways, whereas CFC-BDP was confined to the central airways with little, if any, peripheral airway deposition. A second study with asthmatics (n=16) confirmed that 56% of the HFA-BDP dose was deposited in the airways, with 33% in the oro-pharynx.In conclusion, hydrofluoroalkane-134a-beclomethasone dipropionate deposition was much greater in the airways than chlorofluorocarbon-beclomethasone dipropionate, with a concomitant reduction in oropharyngeal deposition. The increased lung deposition efficiency of the hydrafluoroalkane propellant has led to a reduction in the amount of bedomethasone dipropionate needed to achieve a similar efficacy. The penetration of the hydrofluoroalkane to the small airways may provide asthma treatment not afforded by conventional chlorofluorocarbons.