HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) All Versions of this Article: 0091270009336353v1 49/10/1239    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Google Scholar Articles by Jansat, J. M. Articles by Gurniak, M. PubMed PubMed Citation Articles by Jansat, J. M. Articles by Gurniak, M. Social Bookmarking                         What's this?

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

From Laboratorios Almirall, SA, Barcelona, Spain (Dr Jansat, Dr Lamarca, Dr de Miquel); FOCUS Clinical Drug Development GmbH, Neuss, Germany (Dr Schrödter, Mr Gurniak); and CenTrial GmbH, Tübingen, Germany (Dr Miletzki).

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.

Key Words: Aclidinium bromide • anticholinergic • COPD • multidose • pharmacokinetics

Address for reprints: Josep Maria Jansat, PhD, Head of Bioanalysis and Pharmacokinetics, Laboratorios Almirall, SA, Research Centre, Laureà Miró 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain; e-mail: josep.maria.jansat{at}almirall.com.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?