Mehta Rashmi, Montembault Mickael, Warren Francis, Gupta Ashutosh, Brealey Noushin, Moore Alison
1 GlaxoSmithKline, Research Triangle Park , North Carolina, United States .
2 GlaxoSmithKline , Stockley Park, Uxbridge, United Kingdom .
J Aerosol Med Pulm Drug Deliv. 2016 Aug;29(4):386-92. doi: 10.1089/jamp.2015.1236. Epub 2016 Jan 29.
The Mini Spacer has been developed for use with Ventolin(®) metered dose inhalers (MDIs) to improve accessibility to affordable spacers in developing countries. To ensure patient safety is not compromised if the Mini Spacer is used off-label with fluticasone propionate (FP) or salmeterol/FP combination (SFC) MDIs (currently not recommended), this study compared the systemic exposure of FP and salmeterol following delivery of FP and SFC MDIs with the Mini Spacer and the Aerochamber Plus(®) spacer (Aerochamber).
This was an open-label, randomized, single dose, crossover study in healthy subjects that evaluated four treatments: i) FP 250 μg MDI with Mini Spacer; ii) FP 250 μg MDI with Aerochamber; iii) SFC 25/250 μg with Mini Spacer; iv) SFC 25/250 μg with Aerochamber. There was a minimum 7 day washout between treatments. Pharmacokinetic samples were collected over 24 hours post-dose. The co-primary endpoints were FP area under the concentration-time curve from time zero to 24 h [FP AUC(0-24)] and salmeterol maximum plasma concentration [Cmax].
FP systemic exposure in terms of AUC(0-24) was lower following inhalation with the Mini Spacer compared with the Aerochamber for both FP 250 μg (Mini Spacer/Aerochamber Ratio 0.76 [90% CI: 0.57-1.01]) and SFC 25/250 μg (Ratio 0.74 [90% CI: 0.56-0.99]). Salmeterol systemic exposure was also lower following SFC 25/250 μg with Mini Spacer compared with Aerochamber (Cmax Ratio 0.90 [90% CI 0.48-1.66]). The incidence of adverse events was low and similar with each treatment.
In the event of use of the Mini Spacer with FP and SFC MDIs, which is not recommended, FP and salmeterol systemic exposure is unlikely to be higher than if MDIs were to be used with the Aerochamber. However, these data do not indicate that the Mini Spacer and Aerochamber are interchangeable.
已开发出迷你储雾罐，用于与万托林（®）定量吸入器（MDIs）配合使用，以提高发展中国家患者获得价格合理的储雾罐的机会。为确保在将迷你储雾罐用于丙酸氟替卡松（FP）或沙美特罗/氟替卡松组合（SFC）MDIs（目前不推荐）时患者安全不受影响，本研究比较了使用迷你储雾罐和爱全乐储雾罐（®）（Aerochamber）递送FP和SFC MDIs后FP和沙美特罗的全身暴露情况。
这是一项针对健康受试者的开放标签、随机、单剂量、交叉研究，评估了四种治疗方法：i）250μg FP MDI与迷你储雾罐配合使用；ii）250μg FP MDI与爱全乐储雾罐配合使用；iii）25/250μg SFC与迷你储雾罐配合使用；iv）25/250μg SFC与爱全乐储雾罐配合使用。各治疗之间至少有7天的洗脱期。给药后24小时内采集药代动力学样本。共同主要终点为从时间零点到24小时的FP浓度-时间曲线下面积[FP AUC(0 - 24)]和沙美特罗的最大血浆浓度[Cmax]。
对于250μg FP（迷你储雾罐/爱全乐储雾罐比值0.76 [90% CI：0.57 - 1.01]）和25/250μg SFC（比值0.74 [90% CI：0.56 - 0.99]），使用迷你储雾罐吸入后，FP的全身暴露在AUC(0 - 24)方面低于使用爱全乐储雾罐。与爱全乐储雾罐相比，25/250μg SFC与迷你储雾罐配合使用时沙美特罗的全身暴露也较低（Cmax比值0.90 [90% CI 0.48 - 1.66]）。不良事件的发生率较低，且各治疗组相似。
在不推荐的情况下将迷你储雾罐与FP和SFC MDIs一起使用时，FP和沙美特罗的全身暴露不太可能高于MDIs与爱全乐储雾罐一起使用时。然而，这些数据并不表明迷你储雾罐和爱全乐储雾罐可互换使用。
