哮喘联盟

   摘要
   背景与目的：定量吸入器需要患者协调吸气以配合推药动作。而沙丁胺醇多剂量干粉吸入器(mDPI)则不需要患者呼吸协调配合，因此，简化了沙丁胺醇入肺的过程。本研究旨在比较沙丁胺醇通过ProAir®氢氟烷(HFA)定量吸入器和多剂量吸入器治疗哮喘的疗效、药代学、药效学、肺外药效学及安全性。
   方法：两项双盲、随机、双模拟、交叉、多中心的安慰剂对照研究，纳入对象为持续性哮喘患者。研究1： 47例成人患者分别接受累积剂量的沙丁胺醇mDPI或ProAir®HFA (90 µg/吸; 1 吸+ 1吸 + 2吸 + 4吸 + 8吸)，或安慰剂。研究2：71例年龄12岁以上的患者随机接受沙丁胺醇mDPI 90 μg或180 μg，或ProAir® HFA, 或安慰剂。
   主要疗效终点：每次吸入累积剂量30分钟后的基线校正FEV1(30分钟FEV1)（研究1），用药后6小时内的效应曲线下FEV1面积(FEV1AUEC0-6)（研究2）
   结果：研究1：沙丁胺醇mDPI和ProAir® HFA每次累积剂量用药后FEV1之差及其90%可信区间均在预设值范围内；两者最后一次用药后FEV1 AUEC0-6之差及其90%可信区间也均在预设值范围内。两种治疗方案高剂量与低剂量相比，FEV1相差均有显著意义(p<0.0001)。两种治疗方案的全身性暴露、肺外药效学及安全性相似。研究2：沙丁胺醇mDPI和ProAir® HFA平均FEV1 AUEC0-6显著大于安慰剂(p<0.0001)。而沙丁胺醇mDPI与90 µg和180 µg ProAir® HFA平均FEV1 AUEC0-6相当。两种治疗方案均耐受良好。
   结论：沙丁胺醇mDPI和ProAir® HFA支气管扩张疗效相当，药代/药效学特征类似，安全性与吸入性沙丁胺醇一致。
 

（杨冬 审校）
Clin Drug Investig. 2015 Nov 5. [Epub ahead of print]

 

Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Albuterol (Salbuterol) Multi-dose Dry-Powder Inhaler and ProAir® Hydrofluoroalkane for the Treatment of Persistent Asthma: Results of Two Randomized Double-Blind Studies.
 

Kerwin EM1, Taveras H2, Iverson H2, Wayne D2, Shah T2, Lepore MS3, Miller DS4.
 

Abstract
BACKGROUND AND OBJECTIVE:Metered-dose inhalers require patients to coordinate inhalation with actuation. The present albuterol multi-dose dry-powder inhaler (mDPI) does not require patients to coordinate inspiration with actuation, thereby simplifying delivery of albuterol to the lungs. The aim of the present study was to compare the efficacy, pharmacokinetics, pharmacodynamics, extrapulmonary pharmacodynamics, and safety of albuterol (salbuterol) delivered via a ProAir® hydrofluoroalkane (HFA) metered-dose inhaler and an mDPI.
METHODS:Two double-blind, randomized, double-dummy, crossover, multicenter, placebo-controlled studies in persistent asthma patients were conducted. Study 1: 47 adult patients were treated with cumulative doses of albuterol mDPI or ProAir HFA (90 µg/inhalation; 1 + 1 + 2 + 4 + 8 inhalations) or placebo. Study 2: 71 patients aged ≥12 years were randomly assigned to receive 90 or 180 μg of albuterol mDPI or ProAir HFA, or placebo.
PRIMARY EFFICACY ENDPOINTS : were baseline-adjusted forced expiratory volume in 1 s (FEV1) at 30 min (30-min FEV1) after each cumulative dose (Study 1) and FEV1 area under the effect curve over 6 h (FEV1AUEC0-6) after dosing (Study 2).
RESULTS:Study 1: differences, with corresponding 90 % confidence intervals, between albuterol mDPI and ProAir HFA in FEV1 after each cumulative dose and in FEV1 AUEC0-6 after the final dose were within pre-established equivalence limits. The difference in FEV1 at high vs. low doses was significant for both active treatments (p < 0.0001). Active treatments were similar in systemic exposure, extrapulmonary pharmacodynamics, and safety. Study 2: mean FEV1 AUEC0-6 was significantly greater than for placebo for both doses of albuterol mDPI and ProAir HFA (p < 0.0001). Albuterol mDPI was comparable to ProAir HFA at 90 and 180 µg. Both study treatments were generally well tolerated.
CONCLUSION:The bronchodilatory efficacy and pharmacokinetic/pharmacodynamic profiles of albuterol mDPI and ProAir HFA are comparable, with a safety profile consistent with that of inhaled albuterol.

Clin Drug Investig. 2015 Nov 5. [Epub ahead of print]