title: Pharmacokinetics of aclidinium bromide/formoterol fumarate fixed-dose combination compared with individual components: A phase 1, open-label, single-dose study.
abstract: Inhaled, long-acting bronchodilators represent a cornerstone of maintenance treatment for chronic obstructive pulmonary disease (COPD). Aclidinium bromide/formoterol fumarate 400/12 μg fixed-dose combination (FDC) has recently been licensed for use in adults with COPD in the European Union. This phase 1, randomized, open-label, 3-way, complete crossover, single-dose study assessed the pharmacokinetics, safety, and tolerability of an FDC, aclidinium bromide 400 μg, and formoterol fumarate 12 μg, all administered via Genuair™ to 30 healthy subjects. The rate and extent of absorption were comparable for aclidinium/formoterol FDC and individual monotherapies; aclidinium/formoterol FDC and aclidinium alone: Cmax , 270 and 215 pg/mL, respectively; AUC0-t , 229 and 222 pg · h/mL, respectively; aclidinium/formoterol FDC and formoterol alone: Cmax , 11 and 9.3 pg/mL, respectively; AUC, 36 and 32.4 pg · h/mL, respectively. There were no major differences in relative bioavailability between the combination and monotherapies: the aclidinium Cmax and AUC0-t were 26% and 3% higher, respectively, with aclidinium/formoterol FDC compared with aclidinium alone, and 18% and 11% higher, respectively, compared with formoterol alone. Aclidinium/formoterol FDC was well tolerated; the incidence of adverse events was low and similar to the monotherapies. Aclidinium/formoterol FDC was not associated with any major differences in rate and extent of absorption or relative bioavailability compared with monotherapies.
authors.affiliation: Early Phase Clinical Unit Berlin, PAREXEL International GmbH, Berlin, Germany.
authors.forename: Rainard
authors.initials: R
authors.lastname: Fuhr
authors.affiliation: Formerly of Almirall S.A., Barcelona, Spain.
authors.forename: Anne
authors.initials: A
authors.lastname: Leselbaum
authors.affiliation: R&D Centre, Almirall S.A., Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Aubets
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D000068759:Formoterol Fumarate / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D014326:Tropanes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D014326:Tropanes; C542859:aclidinium bromide; D000068759:Formoterol Fumarate
keywords: aclidinium bromide; chronic obstructive pulmonary disease; fixed-dose combination; formoterol fumarate; pharmacokinetics