Table 4

Suppression by roflumilast and reference PDE4 inhibitors of LPS-induced circulating TNFα in the rat

CompoundED50 p.o.
μmol/kg
Roflumilast0.3 (0.13, 0.51)
N-Oxide0.3 (0.16, 0.63)
Piclamilast2.6 (1.7, 3.9)
Rolipram7.5 (2.9, 19.8)
Cilomilast93.0 (37.7, 230.2)

In vivo effects of p.o. administered roflumilast and itsN-oxide metabolite in comparison with reference PDE4 inhibitors on LPS-induced TNFα in Sprague-Dawley rats. Compounds were given p.o. 1 h prior to and plasma samples for determination of TNFα concentrations were obtained 1.5 h after LPS challenge (0.1 mg/kg i.v.). n = 8–16 per dose; 4 doses per compound. Data are given as means and 95% confidence limits (in parentheses).