Does a single dose of the phosphodiesterase 4 inhibitor, cilomilast (15 mg), induce bronchodilation in patients with chronic obstructive pulmonary disease?

Maintenance treatment with PDE4 inhibitor cilomilast improves FEV1 in chronic obstructive pulmonary disease (COPD) patients. We investigated the acute bronchodilating effects of a single dose of cilomilast with or without concomitant administration of inhaled salbutamol and/or ipratropium bromide in 21 patients with COPD (mean (SD) age 64 (8.1) y, post-salbutamol FEV1 47.7 (13.2) %predicted). FEV1 was measured before and up to 8 hourly intervals after intake of placebo, cilomilast, or cilomilast in combination with inhaled salbutamol 400 jig and/or ipratropium bromide 80 mug. Maximum increase in FEV1 from pre-dose baseline was calculated after each treatment and differences between treatment arms were analyzed by ANOVA. The mean (SEM) maximum increase in FEV1 was 139.6 (18.5) ml following cilomilast and 151.5 (18.5) ml following placebo (95% C.I. for mean difference between cilomilast and placebo:-67.3, 43.6 ml). Furthermore, combined treatment of cilomilast with salbutamol or ipratropium resulted in a maximum increase in FEV1 of 280.7 (25.6) and 297.0 (25.9) ml, respectively, while this was 379.0 (24.6) ml following cilomilast with both salbutamol and ipratropium (p < 0.01). We conclude that a single dose of cilomilast does not produce acute bronchodilation in patients with COPD who otherwise respond to inhaled bronchodilators. Our results implicate that the change in lung function seen after long-term treatment with cilomilast is not the result of acute bronchodilation in patients with COPD. (C) 2003 Elsevier Science Ltd. All rights reserved.