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Safety and Pharmacokinetics of Multiple Doses of Aclidinium Bromide, a Novel Long‐Acting Muscarinic Antagonist for the Treatment of Chronic Obstructive Pulmonary Disease, in Healthy Participants
Author(s) -
Jansat Josep M.,
Lamarca Rosa,
Miquel Gonzalo,
Schrödter Andreas,
Miletzki Barbara,
Gurniak Matthias
Publication year - 2009
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009336353
Subject(s) - pharmacokinetics , tiotropium bromide , bioavailability , pharmacology , copd , metabolite , medicine , placebo , adverse effect , inhaler , pharmacodynamics , anesthesia , asthma , lung , lung function , alternative medicine , pathology
Systemic exposure to anticholinergics used for chronic obstructive pulmonary disease (COPD) may lead to side effects. This study assessed safety, tolerability, and pharmacokinetics of multiple doses of aclidinium bromide, a novel, long‐acting antimuscarinic. Sixteen healthy participants received aclidinium bromide 200, 400, or 800 μg or placebo by dry‐powder inhaler for 5 days, with ≥7 days washout. Aclidinium bromide and metabolite pharmacokinetics were assessed. Aclidinium bromide plasma levels were below the lower limit of quantification (LLOQ: 0.05 ng/mL) after 200 μg and in most participants after 400 μg. Plasma levels in all participants were below the LLOQ at all doses, including the highest dose, beyond 1 hour postdose. AUC 0‐t and C max at steady state were, respectively, 0.08 ng·h/mL and 0.12 ng/mL (aclidinium bromide), 0.40 ng·h/mL and 0.14 ng/mL (alcohol metabolite), and 13.47 ng·h/mL and 2.26 ng/mL (acid metabolite). The t max for aclidinium bromide 800 μg was 15 minutes (first kinetic time point). Adverse event frequency was comparable between treatment groups and placebo. The most commonly reported adverse events, probably treatment related, were coughing (n = 2) and dysphagia (n = 1); 94% of adverse events were mild. These data suggest a low systemic bioavailability and favorable safety profile for aclidinium bromide with repeated dosing for COPD.