title: Cilomilast (Ariflo) does not potentiate the cardiovascular effects of inhaled salbutamol.
abstract: We investigated the safety and potential pharmacodynamic interactions arising from the co-administration of inhaled beta(2)-agonist salbutamol and cilomilast (Ariflo), a new oral phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease and asthma. This was a randomised, double-blind, placebo-controlled, multiple-dose, three-period crossover study involving non-smoking volunteers between the ages of 18 and 50 years. Volunteers were randomly assigned to receive cilomilast plus nebulised salbutamol, cilomilast plus nebulised placebo or placebo plus nebulised salbutamol. Each volunteer received cilomilast (10 mg twice daily) or placebo for 5 days. On day 5, the morning dose of cilomilast or placebo was followed 1 h later with a single dose of nebulised salbutamol (2.5 mg) or placebo. Primary variables were average change from pre- to 1.5 h post-salbutamol or placebo inhalation in blood pressure, pulse rate, 12-lead ECG and total number of heartbeats measured by 4-h Holter ECG. Thirteen volunteers completed the study. There was no evidence of a clinically important pharmacodynamic interaction between cilomilast and salbutamol in healthy volunteers. Both agents were well tolerated. In conclusion, the pharmacodynamic effects associated with salbutamol inhalation were unaffected by co-administration of cilomilast.
authors.affiliation: Clinical Pharmacology, GlaxoSmithKline, Harlow, UK. Robert.D.Murdoch@gsk.com
authors.forename: R D
authors.initials: RD
authors.lastname: Murdoch
authors.forename: H
authors.initials: H
authors.lastname: Cowley
authors.forename: J
authors.initials: J
authors.lastname: Kelly
authors.forename: R
authors.initials: R
authors.lastname: Higgins
authors.forename: D
authors.initials: D
authors.lastname: Webber
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002264:Carboxylic Acids; D018592:Cross-Over Studies; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003509:Cyclohexanecarboxylic Acids; D004311:Double-Blind Method; D004347:Drug Interactions; D015716:Electrocardiography, Ambulatory; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D013997:Time Factors
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; 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; D000420:Albuterol