A proof-of-concept study to evaluate the antiinflammatory effects of a novel soluble cyclodextrin formulation of nebulized budesonide in patients with mild to moderate asthma.
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 microg of Capsitol-Enabled Budesonide Inhalation Solution (CBIS) twice daily or 500 microg 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.
Williamson
Peter A
PA
Asthma and Allergy Research Group, University of Dundee, Dundee, Scotland. p.a.williamson@dundee.ac.uk
Menzies
Daniel
D
Nair
Arun
A
Tutuncu
Ahmet
A
Lipworth
Brian J
BJ
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D019819:Budesonide / Q000627:therapeutic use*; D003505:Cyclodextrins / Q000627:therapeutic use*; D004304:Dosage Forms; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D012995:Solubility; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D003505:Cyclodextrins; D004304:Dosage Forms; D019819:Budesonide