title: Does a single dose of the phosphodiesterase 4 inhibitor, cilomilast (15 mg), induce bronchodilation in patients with chronic obstructive pulmonary disease?
abstract: Maintenance treatment with PDE(4) inhibitor cilomilast improves FEV(1) 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 FEV(1) 47.7 (13.2) %predicted). FEV(1) was measured before and up to 8 hourly intervals after intake of placebo, cilomilast, or cilomilast in combination with inhaled salbutamol 400 microg and/or ipratropium bromide 80 microg. Maximum increase in FEV(1) from pre-dose baseline was calculated after each treatment and differences between treatment arms were analyzed by ANOVA. The mean (SEM) maximum increase in FEV(1) 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 FEV(1) 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.
authors.affiliation: Department of Pulmonology, Leiden University Medical Centre, PO Box 9600, Leiden RC 2300, The Netherlands. d.c.grootendorst@lumc.nl
authors.forename: D C
authors.initials: DC
authors.lastname: Grootendorst
authors.forename: S A
authors.initials: SA
authors.lastname: Gauw
authors.forename: R
authors.initials: R
authors.lastname: Baan
authors.forename: J
authors.initials: J
authors.lastname: Kelly
authors.forename: R D
authors.initials: RD
authors.lastname: Murdoch
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: K F
authors.initials: KF
authors.lastname: Rabe
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000420:Albuterol / Q000008:administration & dosage / Q000627:therapeutic use; D000704:Analysis of Variance; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002264:Carboxylic Acids; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003509:Cyclohexanecarboxylic Acids; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008448:Maximal Expiratory Flow Rate; D008875:Middle Aged; D009570:Nitriles; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*
chemical_list: D001993:Bronchodilator Agents; D002264:Carboxylic Acids; D003509:Cyclohexanecarboxylic Acids; D009570:Nitriles; C433247:Cilomilast; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D009241:Ipratropium; D000420:Albuterol