RESUMEN
BACKGROUND: The short-acting beta(2)-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 (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. RESULTS: 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). 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 FEV(1) and tolerability. Plasma (R)-albuterol levels and mean heart rate were less with levalbuterol HFA MDI.
Asunto(s)
Agonistas Adrenérgicos beta/administración & dosificación , Albuterol/administración & dosificación , Asma/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Administración por Inhalación , Adolescente , Agonistas Adrenérgicos beta/efectos adversos , Agonistas Adrenérgicos beta/sangre , Agonistas Adrenérgicos beta/uso terapéutico , Adulto , Albuterol/efectos adversos , Albuterol/sangre , Albuterol/uso terapéutico , Broncodilatadores/sangre , Broncodilatadores/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Humanos , Hidrocarburos Fluorados/farmacología , Masculino , Inhaladores de Dosis Medida , EspirometríaRESUMEN
The object of this study is a post hoc pairwise comparison of levalbuterol versus racemic albuterol for asthma in a multicenter, double-blind, randomized, placebo-controlled clinical trial. The participants are patients > or =12 years of age (n = 362) with FEV1 45-70% of predicted. The patients received nebulized levalbuterol (0.63 or 1.25 mg), racemic albuterol (1.25 or 2.5 mg), or placebo t.i.d. for 4 weeks. The primary endpoints, published in Nelson HS, Bensch G, Pleskow WW, et al. Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma. J Allergy Clin Immunol 102:943-952, 1998, included comparisons of active treatments with placebo and of the combined levalbuterol with the combined racemic albuterol groups for pulmonary function and rescue medication use. After the first dose, levalbuterol 1.25 mg produced a significantly greater increase in the mean peak change in FEV1 compared with both doses of racemic albuterol (p < 0.03) in all patients and in those with more severe asthma. Levalbuterol 1.25 mg also produced a significantly greater (p < 0.05) mean area under the curve (AUC) of the FEV1 versus time plot (AUC FEV1) compared with all other treatments after the first dose in all patients and in the subset with more severe disease, illustrating better overall improvement in FEV1. Active treatment groups demonstrated significant improvements compared with the placebo group (p < 0.05), except for AUC FEV1 in the racemic albuterol 1.25-mg group at week 4. Levalbuterol in the absence of the (S)-isomer provided greater bronchodilation than the same quantity of (R)-albuterol delivered as the racemate. These data suggest that (S)-albuterol may compromise the efficacy of (R)-albuterol.