The safety and efficacy of nebulized levalbuterol compared with racemic albuterol and placebo in the treatment of asthma in pediatric patients.

Background: Limited dose-response information is available for nebulized beta2 -agonists, especially in young children.

Objective: The purpose of this study was to determine the safety and efficacy of increasing doses of nebulized levalbuterol (Xopenex; the pure R-isomer of racemic albuterol) and racemic albuterol compared with placebo in the treatment of asthma in pediatric patients.

Methods: In this randomized, double-blind, crossover study, children (aged 3 to 11 years) with asthma (resting FEV1 50% to 80% of predicted normal [Polgar's] values) were treated with either levalbuterol, racemic albuterol, or placebo. Eligible subjects underwent a screening visit followed by 4 treatment visits. At each treatment visit, serial pulmonary function tests were completed before and after the treatment; plasma was collected to determine enantiomer levels, and safety was evaluated.

Results: Five 3- to 5-year-old patients and twenty-eight 6- to 11-year-old patients completed the study, and a total of 87 doses of levalbuterol were administered. In the 6- to 11-year-old group, all doses of levalbuterol were significantly greater than placebo in peak change and percent peak change in FEV1 and area under the FEV1 versus time curve (P <.05). The FEV1 values over the 8-hour study period were similar for levalbuterol 0.31 and 0.63 mg and racemic albuterol 2.5 mg and were greatest after levalbuterol 1.25 mg. Median plasma levels of R-albuterol depended on dose and were 0.4, 0.7, 1.2, and 1.0 after levalbuterol 0.31 mg, 0.63 mg, and 1.25 mg and racemic albuterol 2.5 mg, respectively. All patients in the 2.5-mg racemic albuterol arm had measurable plasma levels of S-albuterol, although S-albuterol levels were undetectable in most patients in the levalbuterol arms. In a few patients who received levalbuterol, S-albuterol levels were detected, which was likely because of the use of racemic albuterol as a concomitant medication. All active treatments were well tolerated. beta-Mediated changes in heart rate, potassium, and glucose were dose dependent for all active treatment groups.

Conclusion: Levalbuterol caused a significantly greater increase in FEV1 than placebo, and FEV1 values were comparable with or better than those observed with racemic albuterol. beta-Mediated side effects were lower for an equipotent dose of levalbuterol when compared with racemic albuterol. Treatment with levalbuterol resulted in plasma levels that were dose dependent and had an approximate correlation with pharmacodynamic parameters.