Two withdrawals occurred during placebo treatment . one subject tested positive for cocaine, and one subject had abnormal ECG changes. Allergen Challenge GSK256066 significantly reduced the EAR, inhibiting the fall in both minimum and weighted mean FEV1 selleck inhibitor by 40. 9% and 57. 2% respec tively compared to placebo. GSK256066 also significantly reduced the LAR, attenuating the fall in both minimum and weighted mean FEV1 by 26. 2% and 34. 3% respectively compared to placebo. Methacholine reactivity at 24 hrs post allergen chal lenge was not different after treatment with GSK256066 compared to placebo. the PC20 was 0. 31 compared to 0. 39 mg/mL respectively, geometric mean dou bling dose difference 0. 31. Pulmonary Function and FeNO The FEV1 and FeNO measurements on day 7 at pre dose and 1 hr post dose are shown in tables 2 and 3 respectively.

There was no difference between the treat ments Inhibitors,Modulators,Libraries for either Inhibitors,Modulators,Libraries of these measurements. variation of AUC and Cmax on day 1 of 89% and 68%, respectively reflecting the difficulty in accurate characterisation of pharmacokinetic parameters when measurable concentrations are close to the Inhibitors,Modulators,Libraries limit of detection. Discussion To our knowledge, this is the first study to show that an inhaled PDE4 inhibitor inhibits the response to allergen challenge in asthma. This placebo controlled study demonstrated that GSK256066 administered for 7 days significantly attenuated the fall in lung function in patients with asthma caused by inhaled allergen challenge. GSK256066 had no effect on the secondary endpoints of methacholine reactivity post allergen chal lenge or exhaled nitric oxide.

Nevertheless, the effects of GSK256066 on the allergen response which was the pri mary endpoint indicate that this drug has therapeutic potential for the treatment of asthma. The delivery of this PDE4 inhibitor by inhalation was associated with low Inhibitors,Modulators,Libraries systemic exposure. Larger clinical trials are needed to study the therapeutic index in more detail. Inhaled allergen challenge is a well recognised and robust model that is commonly used to assess the thera peutic potential of novel treatments for asthma. Comparing the results of different allergen challenge studies Inhibitors,Modulators,Libraries should be done with caution, as meth odological details such as the period of measurement of the late response can vary between studies, and individual patient characteristics may dif fer.

The results of the current study are therefore not directly comparable to the previous publication invol ving the orally administered PDE4 inhibitor roflumilast, which inhibited the maximal fall in the EAR and LAR by 14% and Volasertib structure 33% respectively. Inhibition of 40. 9% and 26. 2% respectively were observed in the current study. Direct head to head comparisons would be the best way to compare GSK256066 to roflumilast.