Roflumilast N-oxide, an active metabolite of roflumilast, is an inhibitor of phosphodiesterase 4 (PDE4). It can be combined with formoterol to enhance the antiinflammatory effect of dexamethasone.
Roflumilast N-oxide is a PDE type 4 inhibitor. Co-administration of rifampicin and roflumilast led to a reduction in total PDE4 inhibitory activity of roflumilast by about 58%[2]. The PDE4 inhibitor roflumilast N-oxide acts (over) additively with simvastatin to prevent CSE-induced EMT (epithelial-mesenchymal transition) in WD-HBEC (well-differentiated human bronchial epithelial cells) in vitro[3]. Roflumilast-N-oxide fosters the expression of SPs (Surfactant proteins) in human AEC-II (alveolar epithelial cells type II) via increase of intracellular cAMP levels potentially contributing to improved alveolar host defence and enhanced resolution of inflammation[4]. Roflumilast N-oxide concentration-dependently triggered a rapid and persistent increase in ciliary beat frequency (CBF) and reversed the decrease in CBF following cigarette smoke extract (CSE). Roflumilast N-oxide protected differentiated human bronchial epithelial cells from reduced CBF and loss of ciliated cells following CSE[5]. Single treatment of db/db mice with 10 mg/kg Roflumilast N-oxide enhances plasma glucagon-like peptide-1 (GLP-1) 4-fold. Chronic treatment of db/db mice with Roflumilast N-oxide at 3 mg/kg shows prevention of disease progression. Furthermore, Roflumilast-N-oxide amplifies forskolin-induced insulin release in primary islets. Roflumilast-N-oxide also shows stronger glucose-lowering effects than its parent compound[6].
搜索
