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 be ta(2)-agonists, especially in young children. Objective: The purpose of this study was to determine the safety and effica cy of increasing doses of nebulized levalbuterol (Xopenex; the pure R-isome r 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 [Po lgar's] values) were treated with either levalbuterol, racemic albuterol, o r placebo. Eligible subjects underwent a screening visit followed by 4 trea tment visits. At each treatment visit, serial pulmonary function tests were completed before and after the treatment; plasma was collected to determin e 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 wer e 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 valu es 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 albutero l arm had measurable plasma levels of S-albuterol, although S-albuterol lev els were undetectable in most patients in the levalbuterol arms. In a few p atients who received levalbuterol, S-albuterol levels were detected, which was likely because of the use of racemic albuterol as a concomitant medicat ion. Ail active treatments were well tolerated. beta-Mediated changes in he art rate, potassium, and glucose mere dose dependent for all active treatme nt groups. Conclusion: Levalbuterol caused a significantly greater increase in FEV1 th an placebo, and FEV1 values were comparable with or better than those obser ved with racemic albuterol. beta-Mediated side effects were lower for an eq uipotent dose of levalbuterol when compared with racemic albuterol. Treatme nt with levalbuterol resulted in plasma levels that were dose dependent and had an approximate correlation with pharmacodynamic parameters.