Inhibitory effects of roflumilast and reference PDE4 inhibitors on allergen-induced early airway reaction in the guinea pig
| Compound Dose | Inhibition of OVA-Induced Decrease of Conductance | ED50 p.o. |
|---|---|---|
| % | μmol/kg | |
| Roflumilast | See Table1 | 1.5 (0.5, 4.4) |
| N-Oxide (μmol/kg) | ||
| 1 | 49 (32.5, 67.4)2-160 | |
| 3 | 63 (47.6, 79.4)2-160 | 1.0 (0.9, 1.1) |
| 10 | 77 (64.7, 89.8)2-160 | |
| Piclamilast (μmol/kg) | ||
| 0.1 | 5 (−10, 20) N.S. | |
| 1 | 9 (−6, 25) N.S. | 8.3 (4.1, 16.9) |
| 3 | 33 (17, 49)2-150 | |
| 10 | 52 (4, 17)2-165 | |
| Rolipram (μmol/kg) | ||
| 3 | 4 (−1, 10) | |
| 20 | 30 (10, 49) | 32.5 (25.1, 42.0) |
| 60 | 75 (60, 89) | |
| Cilomilast (μmol/kg) | ||
| 3 | 12 (1, 24)2-150 | |
| 10 | 44 (31, 56)2-165 | 52.2 (16.8, 162.7) |
| 30 | 35 (21, 50)2-150 | |
| 100 | 59 (47, 71)2-165 |
In vivo effects of p.o. administered roflumilast and itsN-oxide metabolite in comparison with reference PDE4 inhibitors (all 1 h prior to antigen challenge) on OVA-induced, not histamine-mediated decrease of airway conductance in anesthetized and mechanically ventilated guinea pigs. Results represent percentage of inhibition. ED50 values are displayed as means and 95% confidence limits (in parentheses) and describe the half-maximal inhibition of the OVA-induced decrease of airway conductance based on AUC (1 to 12 min after challenge); n = 6 animals per compound dose and placebo; 3–4 doses per compound.