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Báo cáo y học: " The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma. | Singh et al. Respiratory Research 2010 11 26 http respiratory-research.eom content 11 1 26 RESPIRATORY RESEARCH RESEARCH Open Access The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma Dave Singh1 2 Frank Petavy3 Alex J Macdonald3 Aili L Lazaar4 Brian J O Connor5 Abstract GSK256066 is a selective phosphodiesterase 4 inhibitor that can be given by inhalation minimising the potential for side effects. We evaluated the effects of GSK256066 on airway responses to allergen challenge in mild asthmatics. Methods In a randomised double blind cross-over study 24 steroid naive atopic asthmatics with both early EAR and late LAR responses to inhaled allergen received inhaled GSK256066 87.5 mcg once per day and placebo for 7 days followed by allergen challenge. Methacholine reactivity was measured 24 h post-allergen. Plasma pharmacokinetics were measured. The primary endpoint was the effect on LAR. Results GSK256066 significantly reduced the LAR attenuating the fall in minimum and weighted mean FEV1 by 26.2 p 0.007 and 34.3 p 0.005 respectively compared to placebo. GSK256066 significantly reduced the EAR inhibiting the fall in minimum and weighted mean FEV1 by 40.9 p 0.014 and 57.2 p 0.014 respectively compared to placebo. There was no effect on pre-allergen FEV1 or methacholine reactivity post allergen. GSK256066 was well tolerated with low systemic exposure plasma levels were not measurable after 4 hours in the majority of subjects. Conclusions GSK256066 demonstrated a protective effect on the EAR and LAR. This is the first inhaled PDE4 inhibitor to show therapeutic potential in asthma. Trial Registration This study is registered on clinicaltrials.gov NCT00380354 Introduction Inhaled corticosteroids are the cornerstone of antiinflammatory treatment in asthma 1 . However many patients remain symptomatic despite high doses of inhaled corticosteroids even when combined with long acting beta agonists 2 3 . New asthma treatments .