Document Detail


Effect of mometasone furoate (MF)/formoterol fumarate (F) combination (MF/F) on late-phase responses in allergen-challenged Brown Norway rats.
MedLine Citation:
PMID:  20937404     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Mometasone furoate (MF)/formoterol fumarate (F) combination is a new inhaIed corticosteroid/long-acting β(2)-adrenergic agonist (ICS/LABA). The purpose of this study was to evaluate the effects of different dose combinations of MF/F on a variety of late-phase responses to aerosolized antigen challenge in ovalbumin sensitized Brown Norway rats. Late-phase responses were assessed by reductions in lung function, measured by forced vital capacity (FVC) and increased numbers of inflammatory cells and pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid of ovalbumin challenged rats. Intratracheal administration of MF/F 5 h before aerosolized ovalbumin challenge inhibited the increase in inflammatory cells, including eosinophils and levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor-α (TNF-α) appearing in the bronchoalveolar lavage fluid 24 h after the antigen challenge. The combination index for inhibition of both inflammatory cells and cytokines was consistently <1 suggesting a synergistic interaction between MF and F. Intratracheal MF/F given 24 h after the aerosolized ovalbumin challenge reversed the reduction in FVC with statistically significant effects seen over a 24 h period after drug whereas MF and F alone reversed the antigen-induced reduction in FVC at selected times only. At 5 h after drug administration, when both MF and F were partially active, the combination index for MF/F was <1 suggesting a synergistic interaction between MF and F for reversal of the lung function. These results demonstrate that MF/F combination inhibits a variety of late-phase responses induced by allergen challenge and it is likely that MF/F will have a significant benefit in clinical asthma to suppress lung inflammation and improve lung function.
Authors:
Richard W Chapman; Aidan K Curran; Aileen House; Jennifer Richard; Brian Salisbury; John C Hunter; John C Anthes; Jonathan E Phillips
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Publication Detail:
Type:  Journal Article     Date:  2010-10-13
Journal Detail:
Title:  Pulmonary pharmacology & therapeutics     Volume:  24     ISSN:  1522-9629     ISO Abbreviation:  Pulm Pharmacol Ther     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9715279     Medline TA:  Pulm Pharmacol Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  67-73     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Bone, Respiratory, Immunology and Dermatology, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA.
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