Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma,☆☆,,★★

Presented in part at the annual meeting of the American Thoracic Society, Chicago, Ill, April 1998.
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Abstract

Background: Racemic albuterol is an equal mixture of (R)-albuterol (levalbuterol), which is responsible for the bronchodilator effect, and (S)-albuterol, which provides no benefit and may be detrimental. Objective: We sought to compare 2 doses of a single enantiomer, levalbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levalbuterol administered as racemic albuterol with placebo in patients with moderate-to-severe asthma. Methods: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV1 after 4 weeks. Results: The change in peak FEV1 response to the first dose in the combined levalbuterol group was significantly greater compared with the combined racemic albuterol group (0.92 and 0.82 L, respectively; P = .03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV1 was similar for levalbuterol 0.63 mg and racemic albuterol 2.5 mg and greatest for levalbuterol 1.25 mg. Racemic albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV1 was seen after levalbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and β-adrenergic side effects after administration of levalbuterol 0.63 mg were reduced relative to levalbuterol 1.25 mg or racemic albuterol 2.5 mg. At week 4, the predose FEV1 value was greatest in patients who received levalbuterol or placebo when compared with those who received racemic albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. Conclusion: Levalbuterol appears to provide a better therapeutic index than the standard dose of racemic albuterol. These results support the concept that (S)-albuterol may have detrimental effects on pulmonary function. (J Allergy Clin Immunol 1998;102:943-52.)

Section snippets

Subjects

Four hundred twenty-four patients at 33 outpatient asthma clinics in the United States (see Appendix) were enrolled in the study. Eligible patients were nonsmoking males or females 12 years of age or older who had at least a 6-month history of chronic and stable asthma (as defined by the American Thoracic Society) requiring pharmacotherapy. Patients were eligible if they had moderate-to-severe lung compromise, defined as an FEV1 between 45% and 70% of predicted normal value for age, gender,

Demographics and disposition

A total of 424 patients enrolled in the study. Sixty-two patients were withdrawn before randomization, 35 (56.5%) of whom did not meet enrollment criteria. Twelve patients (19.4%) voluntarily withdrew, 9 patients (14.5%) were withdrawn because of adverse events (including asthma exacerbation), and 6 patients (9.6%) were lost to follow-up or withdrew for other causes. Of the 362 patients who were randomized into the double-blind treatment period, 328 (90.6%) completed the study and 34 were

DISCUSSION

The effects of the (R)-enantiomer of albuterol, levalbuterol HCl, were compared with those of placebo and standard racemic albuterol in adolescent and adult patients with moderate-to-severe asthma. The study was powered to determine differences between active treatments compared with placebo and was not designed to detect intertreatment differences. Although all of the active treatment arms experienced significant improvement in their FEV1 values compared with placebo, the levalbuterol doses

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    From a the National Jewish Medical and Research Center, Denver; b Allergy, Immunology & Asthma Group, Inc, Stockton; c 317 North El Camino Real, Encinitas; d PPD Pharmaco Inc, Wilmington; and e Sepracor Inc, Marlborough.

    ☆☆

    Supported by a grant from Sepracor Inc, Marlborough, Mass.

    Reprint requests: Harold S. Nelson, MD, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206.

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