Table 3

Inhibitory effects of roflumilast and reference PDE4 inhibitors on late airway inflammation in the BN rat

Parameter, Inhibition of Infiltration/Accumulation/ReleaseED50 p.o. [μmol/kg]
RoflumilastN-OxidePiclamilastRolipramCilomilast
Total cell2.4 (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)
Eosinophil2.7 (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)
Neutrophil2.2 (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)
Lymphocyte2.0 (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)
Protein2.6 (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)
TNFα1.2 (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.