A cumulative dose study of levalbuterol and racemic albuterol administered by hydrofluoroalkane-134a metered-dose inhaler in asthmatic subjects

Background

The short-acting β₂-agonists levalbuterol and racemic albuterol are available for administration through a hydrofluoroalkane-134a (HFA) metered-dose inhaler (MDI).

Objective

This study compared the short-term safety and efficacy of cumulative doses of levalbuterol HFA MDI and racemic albuterol HFA MDI in asthmatic subjects.

Methods

This was a randomized, modified-blind, active-controlled, multicenter, 2-way crossover study. Subjects (n = 49) were randomized to 16 cumulative doses (1×, 2×, 4×, 8×, and 16×) of levalbuterol (45 μg per dose) or racemic albuterol (90 μg 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.

Results

Heart rate and (R)-albuterol exposure increased for both racemic albuterol HFA and levalbuterol HFA. For cumulative doses of 8× or greater, racemic albuterol HFA treatment had greater increases in mean heart rate than levalbuterol HFA (least-squares mean [± SD] difference at the 8× dose was 2.8 beats/min [95% CI, 0.3-5.3] and at the 16× 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. FEV₁ improvements were similar for both treatments. The relative potencies of the 2 therapies, based on FEV₁, were similar (ratio, 1.1 [90% CI, 0.9-1.2]; Finney method).

Conclusion

In this study single-day cumulative dosing of asthmatic subjects with levalbuterol HFA MDI or racemic albuterol HFA MDI resulted in similar improvements in FEV₁ and tolerability. Plasma (R)-albuterol levels and mean heart rate were less with levalbuterol HFA MDI.

Key words: Asthma, safety, efficacy, relative potency, cumulative dose, levalbuterol HFA MDI, racemic albuterol HFA MDI

Abbreviations used: HFA, Hydrofluoroalkane-134a, LS mean, Least-squares mean, MDI, Metered-dose inhaler