Fibrotic diseases are characterized by the accumulation of extracellular matrix together with distortion and disruption of tissue architecture. Phosphodiesterase (PDE)4 inhibitors, by preventing the breakdown of cAMP, can inhibit fibroblast functions and may be able to mitigate tissue remodeling. Transforming growth factor (TGF)-beta1, a mediator of fibrosis, can potentially modulate cAMP by al...

phosphodiesterase-4 inhibitor BAY 19-8004 on lung function and airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). Pulm Pharmacol Ther 2003; 16: 341–347. 5 Hatzelmann A, Morcillo EJ, Lungarella G, et al. The preclinical pharmacology of roflumilast – a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulm Pharmaco...

BACKGROUND β2-adrenoceptor agonists have been shown to reduce the lipopolysaccharide (LPS)-induced cytokine release by human monocyte-derived macrophages (MDMs). We compare the expression of β2-adrenoceptors and the inhibitory effect of formoterol and salmeterol on the LPS-induced release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and a range of chemokines (CCL2, 3, 4, and IL-8...

A sensitive and reliable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) was developed and validated for simultaneous quantification IC87114, roflumilast (RFM), and its active metabolite roflumilast N-oxide (RFN) using tolbutamide as an internal standard. The analytes were extracted by using liquid-liquid extraction and separated on a reverse phase C(18) column (50 mm × 3 mm...

Fibrotic diseases are characterized by the accumulation of extracellular matrix together with distortion and disruption of tissue architecture. Phosphodiesterase 4 (PDE4) inhibitors, by preventing the breakdown of cyclic AMP, can inhibit fibroblast functions and may be able to mitigate tissue remodeling. TGF-β1, a mediator of fibrosis, can potentially modulate cAMP by altering PGE2 metabolism. ...

A forced degradation study on roflumilast drug substance was conducted under the conditions of hydrolysis, oxidation, thermal and photolysis. The method was developed and optimized by analyzing forcefully degraded samples. The best separation was achieved on a Zorbax SB C18 1.8 µm column with 0.005 M ammonium formate buffer pH 3.5 and acetonitrile as mobile phase in a 13 min run time. The propo...

Agents which increase intracellular cyclic adenosine monophosphate (cAMP) may have an antagonistic effect on pro-inflammatory molecule production so that inhibitors of the cAMP degrading phosphodiesterases have been identified as promising drugs in chronic inflammatory disorders. Although many such inhibitors have been developed, their introduction in the clinic has been hampered by their narro...