This study marks the r M Possible additionally USEFUL PDE4 isoforms in the regulation of a Llergic airway inflammation, and the need for more than one isoform of ICG-001 PDE4 inhibition by the reaction Atemwegshyperreaktivit t And allergic inflammatory remodeling wildtype M Nozzles  such as rolipram and roflumilast. Many pr Clinical studies, the anti-inflammatory potential of PDE4 inhibitors in models of allergic inflammation and in human cells in vitro, were best to a certain extent, In clinical trials in patients with asthma CONFIRMS. Treatment twice t Possible for 9.5 days with CDP840 PDE4 inhibitor prevents the development of the Sp Tphasenreaktion in asthmatics 30%. A Much the same extent inhibition of Sp tphasenreaktion was observed after the treatment once a day for 7 to 10 days roflumilast.
This Sp tphasenreaktion Used by clinicians model the Limonin inflammatory response to an insult allergic airway. In both studies, the effects of the drug Sen treatment of acute bronchoconstriction Allergen was modest and is compatible with the absence of any detectable effect PDE4 inhibition on mast cell function and highlight the r The other PDE enzymes, n Namely PDE3 in the bronchial smooth muscle relaxation. Hyperreaktivit was t not diminished by these drugs, even if a subsequent study tended modest protection against allergen-induced Atemwegshyperreaktivit t, suggesting l Sst that PDE4 can no appropriate target for this particular Ph His show phenomenon or that h here doses are needed to complement hrleisten re and sustained inhibition of the enzyme by weight attenuator and thus chung Hyperreaktivit t.
It is interesting that roflumilast has a plasma half-life of 16 hours after a single oral administration and by CYP3A4 to N-oxide metabolized metabolites which favor a much h Here bioavailability with a half-life 20 hours, the enzyme exposure. Expect these favorable pharmacokinetic profile that produce l Ngere PDE4 inhibition. There was a significant reduction of the activity t of circulating monocytes in patients taking roflumilast maintained for 4 weeks, w While the extent these change was small, which then causes. a reduction of about 1.3 times the tumor necrosis factor by monocytes in dependence dependence of endotoxin in vitro Therefore, it is doubtful that the total amount of PDE4 inhibition can be achieved in cells used in tissue compartment of the airway at the dose in clinical trials.
The side effects on the h Were reported most common, headache, nausea and diarrhea of mild to m were Safe and suggest that if the benefit / risk ratio Can be improved ratio, it can also complicate the use of these drugs in asthma. This is a worthwhile goal to pursue in light of the clinical study, similar clinical efficacy between roflumilast and beclomethasone dipropionate reported in patients with persistent asthma. PDE4 COPD and chronic obstructive pulmonary disease, unlike asthma is caused by smoking, although in the developing br Change smoke from biomass Lant is also a risk factor.