Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Dec 2012
Randomized Controlled Trial Multicenter Study28-Day safety and tolerability of umeclidinium in combination with vilanterol in COPD: a randomized placebo-controlled trial.
Umeclidinium (UMEC; GSK573719) is a new long-acting muscarinic antagonist (LAMA) currently in development in combination with vilanterol (VI), an inhaled, long-acting beta₂ agonist for the treatment of chronic obstructive pulmonary disease (COPD). The primary aim of this study was to evaluate the safety and tolerability of repeat dosing of UMEC and VI in combination once daily for 28 days in patients with COPD. ⋯ Once-daily dosing with UMEC in combination with VI in patients with moderate-to-very-severe COPD was well tolerated over 28 days.
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Pulm Pharmacol Ther · Dec 2012
Comparative StudyA comparison of antiasthma drugs between acute and chronic ovalbumin-challenged guinea-pig models of asthma.
Pre-clinical evaluation of asthma therapies requires animal models of chronic airways inflammation, airway hyperresponsiveness (AHR) and lung remodelling that accurately predict drug effectiveness in human asthma. However, most animal models focus on acute allergen challenges where chronic inflammation and airway remodelling are absent. Chronic allergen challenge models have been developed in mice but few studies use guinea-pigs which may be more relevant to humans. ⋯ GW274150 also inhibited the LAR, AHR and eosinophil influx in the acute model, but not, together with the remodelling, in the chronic model. In the clinical setting, inhaled corticosteroids and phosphodiesterase 4 inhibitors are relatively effective against most features of asthma whereas the iNOS inhibitor GW274150 was ineffective. Thus, while there remain certain differences between our data and clinical effectiveness of these antiasthma drugs, a chronic pulmonary inflammation guinea-pig model does appear to be a better pre-clinical predictor of potential asthma therapeutics than an acute model.