The aim of this study was to investigate whether treatment with a low daily dose of 400 µg inhaled budesonide (Pulmicort® Turbuhaler®) in newly diagnosed asthmatics could influence the course of asthma.Seventy five adult patients, mostly with mild asthma, diagnosed during the previous year and bronchial hyperresponsiveness, participated in a double-blind, randomized, parallel-group multicentre study. They were treated with budesonide 200 µg b.i.d. or placebo, delivered via Turbuhaler® for 12 months and followed-up for another 6 months without inhaled steroid treatment. Airway function, symptom scores, reactivity to histamine and inflammatory indices in blood were assessed.The mean increase in morning peak expiratory flow (PEF) was 28 L·min -1 after budesonide treatment compared with no increase in the placebo group (p=0.011). The provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) (geometric mean) increased in the budesonide group by approximately two doubling dose steps, but not in the placebo group (p=0.0003). The difference between groups with regard to improvement in asthma symptom scores and inflammatory indices did not reach statistical significance. During the 6 month follow-up, the PEF values of the patients who had previously been treated with budesonide decreased by 18 L·min -1 while the PD20 decreased by approximately one doubling dose step.In conclusion, early treatment with a low dose of budesonide improves airway function and decreases bronchial responsiveness, but the improvements are shortlasting without continued treatment.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Chlorofluorocarbons (CFCs) have been implicated in damage to the ozone layer, and are due to be phased out in accordance with the Montreal Protocol.• Hydrofluoroalkane-134a (HFA) has been found to act as an adequate propellant for pressurized metered-dose inhaler delivery systems without the same deleterious environmental effects. WHAT THIS STUDY ADDS• This paper presents data from both steady-state pharmacokinetic and pharmacodynamic assessments of HFA vs. CFC pressurized metered-dose inhaler formulations of budesonide. It demonstrates that they are therapeutically equivalent in terms of relative lung bioavailability, airway efficacy and systemic effects. AIMSA hydrofluoroalkane formulation of budesonide pressurized metered-dose inhaler has been developed to replace the existing chlorofluorocarbon one. The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic characteristics of both formulations. METHODSSystemic bioavailability and bioactivity of both hydrofluoroalkane and chlorofluorocarbon pressurized metered-dose inhaler formulations at 800 mg twice daily was determined during a randomized crossover systemic pharmacokinetic/pharmacodynamic study at steady state in healthy volunteers. Measurements included the following: plasma cortisol AUC24h [area under the concentration-time curve (0-24 h)], budesonide AUC0-12h and Cmax. Clinical efficacy was determined during a randomized crossover pharmacodynamic study in asthmatic patients receiving 200 mg followed by 800 mg budesonide via chlorofluorocarbon or hydrofluoroalkane pressurized metered-dose inhaler each for 4 weeks. Methacholine PC20 (primary outcome), exhaled nitric oxide, spirometry, peak expiratory flow and symptoms were evaluated. RESULTSIn the pharmacokinetic study, there were no differences in cortisol, AUC0-12h [area under the concentration-time curve (0-12 h)], Tmax (time to maximum concentration) or Cmax (peak serum concentration) between the hydrofluoroalkane and chlorofluorocarbon pressurized metered-dose inhaler. The ratio of budesonide hydrofluoroalkane vs. chlorofluorocarbon pressurized metered-dose inhaler for cortisol AUC24h was 1.02 (95% confidence interval 0.93-1.11) and budesonide AUC0-12h was 1.03 (90% confidence interval 0.9-1.18). In the asthma pharmacodynamic study, there was a significant dose response (P < 0.0001) for methacholine PC20 (provocative concentration of methacholine needed to produce a 20% fall in FEV1) with a relative potency ratio of 1.10 (95% confidence interval 0.49-2.66), and no difference at either dose. No significant differences between formulations were seen with the secondary outcome variables. CONCLUSIONSHydrofluoroalkane and chlorofluorocarbon formulations of budesonide were therapeutically equivalent in terms of relative lung bioavailability, airway efficacy and systemic effects.

Treatment with budesonide HFA pMDI is effective and well tolerated in children with asthma and is clinically comparable to budesonide CFC pMDI.

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