title: Therapeutic ratio of inhaled corticosteroids in adult asthma. A dose-range comparison between fluticasone propionate and budesonide, measuring their effect on bronchial hyperresponsiveness and adrenal cortex function.
abstract: Inhaled corticosteroids have become the mainstay treatment of bronchial asthma. However, simultaneous evaluations of efficacy and side effects are few. This study aimed to compare the relative effect of fluticasone propionate (FP) and budesonide (BUD) on bronchial responsiveness and endogenous cortisol secretion in adults with asthma. The study was double-blind and included 66 adults with asthma, who were randomized to FP (n = 33) or BUD (n = 33). Prestudy, all participants were clinically stable, using inhaled corticosteroids and hyperresponsive to methacholine. Eligible patients were randomized to three consecutive 2-wk periods with either FP 250 microg twice daily, FP 500 microg twice daily, and FP 1,000 microg twice daily, or BUD 400 microg twice daily, BUD 800 microg twice daily, and BUD 1,600 microg twice daily, delivered by Diskhaler and Turbuhaler, respectively. Before randomization and at the end of each treatment, bronchial methacholine PD(20), 24-h urinary cortisol excretion (24-h UC), plasma cortisol, serum osteocalcin, and blood eosinophils were determined. The relative PD(20) potency between FP and BUD was 2.51 (95% CI, 1.05-5.99; p < 0. 05), while the relative 24-h UC potency was 0.60 (95% CI, 0.44-0.83; p < 0.01). The differential therapeutic ratio (FP/BUD) based on PD(20) potency and 24-h UC was 4.18 (95% CI, 1.16-15.03; p < 0.05). The difference in systemic potency was also seen for plasma cortisol, serum osteocalcin, and blood eosinophils. Therapeutic ratio over a wide dose range, determined by impact on bronchial responsiveness and endogenous corticosteroid production, seems to favor FP.
authors: Department of Respiratory Diseases, Aarhus University Hospital, Aarhus, Denmark. lpn@dadlnet.dk
authors: L P
authors: LP
authors: Nielsen
authors: R
authors: R
authors: Dahl
mesh_terms: D000280:Administration, Inhalation; D000302:Adrenal Cortex / Q000187:drug effects* / Q000503:physiopathology; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000494:pharmacology; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology; D019819:Budesonide / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008297:Male; D013997:Time Factors
chemical_list: D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D019819:Budesonide; D000068298:Fluticasone