Airway and systemic effects of hydrofluoroalkane fluticasone and beclomethasone in patients with asthma.
BACKGROUND
With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses.


METHODS
Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 micro g/day followed by 1000 micro g/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV(1)) of 20% or more (methacholine PD(20)) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC).


RESULTS
For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD(20) compared with baseline. The improvement was not significantly greater with 1000 micro g/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p<0.05) lower values at 1000 micro g/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)).


CONCLUSIONS
There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 micro g/day. At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.
D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D003404:Creatinine / Q000378:metabolism; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D000068298:Fluticasone; D005540:Forced Expiratory Flow Rates; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage*; D006854:Hydrocortisone / Q000652:urine; D008297:Male; D016210:Methacholine Chloride; D005466:Fluorocarbons
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D001507:Beclomethasone; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D003404:Creatinine; D000068298:Fluticasone; D006845:Hydrocarbons, Fluorinated; D006854:Hydrocortisone; D016210:Methacholine Chloride; C094049:apaflurane; D005466:Fluorocarbons