Selectivity of roflumilast, its major metabolite and cilomilast for inhibition of phosphodiesterase(PDE)4 activity
| Roflumilast | N-oxide | Cilomilast | |
| PDE1 | >10 | >10 | 74 |
| PDE2 | >10 | >10 | 65 |
| PDE3 | >10 | >10 | >100 |
| PDE4 | 0.0008 | 0.002 | 0.12 |
| PDE5 | 8 | >10 | 83 |
Data are given as mean 50% inhibitory concentrations (IC50) values (µmol·L−1) calculated from concentration–inhibition curves by nonlinear regression analysis. Roflumilast inhibits PDE4 activity from human neutrophils with an IC50 value of 0.8 nM without affecting PDE1 (bovine brain), PDE2 (rat heart), and PDE3 and PDE5 (human platelets), even at 10,000-fold higher concentrations. Roflumilast is almost equipotent to its major metabolite formed in vivo (roflumilast N-oxide) and >100-fold more potent than cilomilast. Data from [14].