Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Aug 2010
ReviewThe preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease.
After more than two decades of research into phosphodiesterase 4 (PDE4) inhibitors, roflumilast (3-cyclopropylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]-benzamide) may become the first agent in this class to be approved for patient treatment worldwide. Within the PDE family of 11 known isoenzymes, roflumilast is selective for PDE4, showing balanced selectivity for subtypes A-D, and is of high subnanomolar potency. The active principle of roflumilast in man is its dichloropyridyl N-oxide metabolite, which has similar potency as a PDE4 inhibitor as the parent compound. ⋯ In summary, roflumilast may be the first-in-class PDE4 inhibitor for COPD therapy. In addition to being a non-steroid, anti-inflammatory drug designed to target pulmonary inflammation, the preclinical pharmacology described in this review points to a broad functional mode of action of roflumilast that putatively addresses additional COPD mechanisms. This enables roflumilast to offer effective, oral maintenance treatment for COPD, with an acceptable tolerability profile and the potential to favourably affect the extrapulmonary effects of the disease.
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Pulm Pharmacol Ther · Aug 2010
Experimental pulmonary infection and colonization of Haemophilus influenzae in emphysematous hamsters.
Bacterial infection has been considered the main cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, experimental model of COPD exacerbation induced by Haemophilus influenzae infection was not available up to now. Furthermore, only a few studies on evaluation of antibiotics using an H. influenzae infection model in mice have been reported. The aim of this work was to evaluate the activity of moxifloxacin on experimental pulmonary infection and colonization of H. influenzae in emphysematous hamsters. ⋯ Our results suggest that chronic bacterial infection and colonization is highly correlated with lung emphysematous lesions, which would be one of the important mechanisms for repeated attacks of acute exacerbations of chronic pulmonary diseases and uncertain efficacies of antibiotics.