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Localized Delivery of PDE-4 Inhibitors to Open the Therapeutic Window

The Localized delivery of phosphodiesterase-4 (PDE-4) inhibitors appears to be short term solution to overcome the dose-limiting side effects of severe nausea and emesis occurring after oral administration. In the long-term, subtype-selective PDE-4 inhibitors and combination regimens may help to improve the therapeutic index.

Barcelona, Spain, May 31, 2006 --( The Business Intelligence firm La Merie S.L. reported today that application of PDE-4 inhibitors as inhaled treatment for bronchial asthma and chronic obstructive pulmonary disease (COPD) or as nasal suspension for the treatment of allergic rhinitis are increasingly used clinical options to avoid dose-limiting side effects of severe nausea and vomiting seen with oral administration. Furthermore, topical administration of PDE-4 inhibitors is evaluated in atopic dermatitis and allergic conjunctivitis. Further clinical uses of PDE-4 inhibitors are inflammatory diseases such as rheumatoid arthritis and ulcerative colitis apart from memory disorders such as Alzheimer’s disease. These results and more were found in a competitor analysis conducted by La Merie Business Intelligence. The findings of the search can be acquired at, La Merie’s News Center and Online Store.

Most of the orally delivered PDE-4 inhibitors to treat asthma and COPD did not make it beyond phase II clinical studies. The major challenge is a narrow therapeutic index caused by dose-limiting side effects, including severe nausea and emesis. The two PDE-4 inhibitors which reached the registration phase were either withdrawn from the MAA process (roflumilast) or received an approvable letter requesting additional confirmatory trial data. The interest in PDE-4 inhibitors still is high as reflected by at least five ongoing development projects in pulmonary & respiratory diseases. The anti-inflammatory properties of PDE-4 inhibitors are also evaluated in atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and ulcerative colitis. Several companies are specifically searching for PDE-4 inhibitors in memory disorders and ischemic stroke.

Non-selective PDE-4 inhibitors, multi-PDE inhibitors and dual M3/PDE-4 blockers are also evaluated in a variety of inflammatory indications including multiple sclerosis, psoriasis, COPD/asthma and cystitis. Most of the inhibitors are small molecules, but antisense may be used for inhalation treatment.

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About La Merie
La Merie S.L. is a Business Intelligence enterprise fully dedicated to provide high quality R&D information to the biopharmaceutical industry. La Merie offers individual consultancy services and publishes reports and periodicals. For more information visit

SOURCE: La Merie Business Intelligence

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