Tripp Kenneth, McVicar William K, Nair Parameswaran, Corren Jonathan, Pleskow Warren W, Goodwin Elizabeth, Baumgartner Rudolf A, Hanrahan John P
Sepracor, Inc, Marlborough, MA 01752, USA.
J Allergy Clin Immunol. 2008 Sep;122(3):544-9. doi: 10.1016/j.jaci.2008.06.015. Epub 2008 Aug 9.
The short-acting beta(2)-agonists levalbuterol and racemic albuterol are available for administration through a hydrofluoroalkane-134a (HFA) metered-dose inhaler (MDI).
This study compared the short-term safety and efficacy of cumulative doses of levalbuterol HFA MDI and racemic albuterol HFA MDI in asthmatic subjects.
This was a randomized, modified-blind, active-controlled, multicenter, 2-way crossover study. Subjects (n = 49) were randomized to 16 cumulative doses (1x, 2x, 4x, 8x, and 16x) of levalbuterol (45 microg per dose) or racemic albuterol (90 microg per dose) administered over a 2-hour period. After a 7-day washout period, subjects were crossed over to the other treatment. After each dose, safety outcomes and pulmonary function were assessed.
Heart rate and (R)-albuterol exposure increased for both racemic albuterol HFA and levalbuterol HFA. For cumulative doses of 8x or greater, racemic albuterol HFA treatment had greater increases in mean heart rate than levalbuterol HFA (least-squares mean [+/- SD] difference at the 8x dose was 2.8 beats/min [95% CI, 0.3-5.3] and at the 16x dose was 3.5 beats/min [95% CI, 0.6-6.4]). (R)-albuterol plasma levels ranged from 10% to 18% higher after racemic albuterol HFA MDI dosing versus after levalbuterol HFA MDI. FEV(1) improvements were similar for both treatments. The relative potencies of the 2 therapies, based on FEV(1), were similar (ratio, 1.1 [90% CI, 0.9-1.2]; Finney method).
In this study single-day cumulative dosing of asthmatic subjects with levalbuterol HFA MDI or racemic albuterol HFA MDI resulted in similar improvements in FEV(1) and tolerability. Plasma (R)-albuterol levels and mean heart rate were less with levalbuterol HFA MDI.
短效β₂受体激动剂左沙丁胺醇和消旋沙丁胺醇可通过氢氟烷烃-134a（HFA）定量吸入器（MDI）给药。
本研究比较了哮喘患者中左沙丁胺醇HFA MDI和消旋沙丁胺醇HFA MDI累积剂量的短期安全性和有效性。
这是一项随机、改良盲法、活性对照、多中心、双向交叉研究。受试者（n = 49）被随机分配接受16种累积剂量（1倍、2倍、4倍、8倍和16倍）的左沙丁胺醇（每剂量45微克）或消旋沙丁胺醇（每剂量90微克），在2小时内给药。经过7天的洗脱期后，受试者交叉接受另一种治疗。每次给药后，评估安全性结果和肺功能。
消旋沙丁胺醇HFA和左沙丁胺醇HFA的心率和（R）-沙丁胺醇暴露量均增加。对于8倍或更高的累积剂量，消旋沙丁胺醇HFA治疗的平均心率增加幅度大于左沙丁胺醇HFA（8倍剂量时的最小二乘均值[±标准差]差异为2.8次/分钟[95%置信区间，0.3 - 5.3]，16倍剂量时为3.5次/分钟[95%置信区间，0.6 - 6.4]）。消旋沙丁胺醇HFA MDI给药后（R）-沙丁胺醇血浆水平比左沙丁胺醇HFA MDI给药后高10%至18%。两种治疗的FEV₁改善情况相似。基于FEV₁的两种疗法的相对效价相似（比值，1.1 [90%置信区间，0.9 - 1.2]；芬尼法）。
在本研究中，哮喘患者单日使用左沙丁胺醇HFA MDI或消旋沙丁胺醇HFA MDI累积给药导致FEV₁和耐受性有相似的改善。左沙丁胺醇HFA MDI的血浆（R）-沙丁胺醇水平和平均心率较低。
