Inhibitory effects of roflumilast and reference PDE4 inhibitors on late airway inflammation in the BN rat
| Parameter, Inhibition of Infiltration/Accumulation/Release | ED50 p.o. [μmol/kg] | ||||
|---|---|---|---|---|---|
| Roflumilast | N-Oxide | Piclamilast | Rolipram | Cilomilast | |
| Total cell | 2.4 (0.39, 15.2) | 1.9 (1.4, 2.4) | 21.3 (14.2, 31.9) | 15.7 (8.0, 31.0) | 98.7 (78.6, 124) |
| Eosinophil | 2.7 (0.1, 71.7) | 2.5 (1.9, 3.3) | 23.8 (14.8, 38.4) | 16.9 (8.1, 35.1) | 106 (80.7, 139) |
| Neutrophil | 2.2 (1.4, 3.4) | 1.8 (1.4, 2.3) | 14.1 (9.9, 20.1) | 16.0 (8.6, 29.7) | 90.0 (67.8, 120) |
| Lymphocyte | 2.0 (1.4, 2.7) | 1.6 (1.3, 1.9) | 19.5 (13.6, 27.9) | 30.6 (13.3, 70.4) | 164 (109, 247) |
| Protein | 2.6 (1.9, 3.7) | 1.8 (1.4, 2.2) | 19.2 (14.5, 25.5) | 14.8 (8.2, 26.6) | 76.9 (62.5, 94.8) |
| TNFα | 1.2 (0.5, 2.6) | 1.6 (0.9, 2.7) | 14.4 (8.6, 24.1) | 9.9 (N.C.) | 71.2 (48.8, 103.8) |
The table summarizes the in vivo efficacy of p.o. administered roflumilast and its N-oxide metabolite in comparison with reference compounds in the OVA-challenged BN rat. Inhibitory effects on OVA-induced cell infiltration, protein accumulation, and TNFα release (measured in BALF) at 48 h postchallenge are displayed. The ED50 values were taken from fitted dose-response curves by log-linear regression analysis as described under Experimental Procedures and are displayed as means and 95% confidence limits (in parentheses). For cell counts and protein detection, number of animals per compound dose as described in the legend to Fig. 4. For TNFα measurement, n = 8–16 per compound dose; 3–4 doses per ED50 value.
N.C., not calculable.