A proof-of-concept study to evaluate the anti-inflammatory effects of a novel soluble cyclodextrin formulation of nebulized budesonide in patients with mild to moderate asthma

Peter A. Williamson, Daniel Menzies, Arun Nair, Ahmet Tutuncu, Brian J. Lipworth

    Research output: Contribution to journalArticle

    Abstract

    Background: A cyclodextrin solution formulation of budesonide has been developed.

    Objective: To assess the anti-inflammatory effect of a novel soluble formulation of nebulized budesonide compared with the present suspension formulation based on a 1:4 nominal dose ratio.

    Methods: Seventeen mild to moderate asthmatic patients were randomized to receive 120 mu g of Capsitol-Enabled Budesonide Inhalation Solution (CBIS) twice daily or 500 mu g of budesonide suspension (Pulmicort Respules) twice daily via nebulizer for 2 weeks in a crossover manner. Methacholine challenge, fractionated exhaled nitric oxide (NO) measurement, spirometry, and 10-hour overnight urinary creatinine-corrected cortisol measurement were conducted at baseline and after each treatment.

    Results: Neither CBIS nor Pulmicort significantly improved the provocation concentration of methacholine that caused a decrease in FEV1 of 10% as change from baseline (doubling dilution changes, 0.82; 95% confidence interval [CI], -0.08 to 1.72; P = .08; and 0.86; 95% CI, -0.61 to 2.32; P = .41, respectively). Both CBIS and Pulmicort suppressed exhaled NO from baseline (geometric mean fold ratios: for tidal NO, 0.70; 95% CI, 0.55-0.90; P = .006; and 0.62; 95% CI, 0.50-0.76; P < .001, respectively; for bronchial flux, 0.73; 95% CI, 0.56-0.95; P = .02; and 0.54; 95% CI, 0.39-0.74; P < .001, respectively). Alveolar NO was significantly suppressed by CBIS (geometric mean fold ratio, 0.33; 95% CI, 0.13-0.85; P = .02) but not by Pulmicort (0.66; 95% CI, 0.25-1.76; P = .81). The mean (SEM) nebulization time for CBIS was 84 (3.0) seconds and for Pulmicort was 303 (19) seconds (P < .001). There were no differences between CBIS and Pulmicort for any other outcome.

    Conclusions: There are no significant differences between formulations for any inflammatory outcome. CBIS has a shorter nebulization time and is given at a quarter of the nominal dose of Pulmicort.

    Original languageEnglish
    Pages (from-to)161-167
    Number of pages7
    JournalAnnals of Allergy, Asthma & Immunology
    Volume102
    Issue number2
    Publication statusPublished - Feb 2009

    Keywords

    • Exhaled nitric oxide
    • Randomized controlled trial
    • Exchanged dynamics
    • Alveolar
    • Methacholine
    • Inflammation
    • Hyperresponsiveness
    • Hydrofluoroalkane
    • Responsiveness
    • Management

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