PMID- 19640353
OWN - NLM
STAT- MEDLINE
DCOM- 20090820
LR  - 20190608
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 47
IP  - 7
DP  - 2009 Jul
TI  - Safety and pharmacokinetics of single doses of aclidinium bromide, a novel 
      long-acting, inhaled antimuscarinic, in healthy subjects.
PG  - 460-8
AB  - OBJECTIVE: Aclidinium bromide is a novel antimuscarinic being developed for the 
      treatment of chronic obstructive pulmonary disease. The objective of this Phase I 
      study was to determine the maximum tolerated dose (MTD) as well as the 
      tolerability, safety and pharmacokinetics of aclidinium in healthy subjects. 
      MATERIALS AND METHODS: 16 healthy subjects were randomized to receive 5 single 
      ascending doses of aclidinium 600 - 6,000 microg or placebo inhaled via dry 
      powder inhaler, with 7 day washouts. Safety measurements included adverse events 
      (AEs), physical examination, vital signs, pupillometry examination, clinical 
      laboratory tests, and 12-lead electrocardiogram. Pharmacokinetic parameters of 
      aclidinium and its metabolites were assessed. RESULTS: The incidence of AEs was 
      comparable between aclidinium and placebo at all doses. Most AEs were mild to 
      moderate with no dose-related or anticholinergic/cardiac AEs. At doses >or= 2,400 
      microg, only 13 AEs were considered treatment related. Aclidinium (600 - 6,000 
      microg) did not produce function-limiting or severe AEs in >or= 50% of subjects; 
      hence, the prospectively-defined MTD was not established. Aclidinium was rapidly 
      converted in plasma into alcohol and carboxylic acid metabolites, and was no 
      longer detectable after 3 hours post-dose for all doses. At lower doses, 
      aclidinium was quantifiable only up to 1 hour post-dose in the majority of 
      subjects. Maximum plasma concentrations for aclidinium were reached within 5 - 7 
      minutes (all doses) and declined rapidly. Mean elimination half-lives of 
      aclidinium > 2,400 microg were approximately 1 hour. AUC and Cmax increased 
      proportionately up to 4,800 microg. CONCLUSIONS: Aclidinium appears to be safe 
      and well tolerated in single doses of 600 - 6,000 microg.
FAU - Jansat, J M
AU  - Jansat JM
AD  - Laboratorios Almirall, SA, Barcelona, Spain. josep.maria.jansat@almirall.es
FAU - Lamarca, R
AU  - Lamarca R
FAU - Garcia Gil, E
AU  - Garcia Gil E
FAU - Ferrer, P
AU  - Ferrer P
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Tropanes)
RN  - UQW7UF9N91 (aclidinium bromide)
SB  - IM
MH  - Administration, Inhalation
MH  - Adult
MH  - Aged
MH  - Area Under Curve
MH  - Delayed-Action Preparations
MH  - Dose-Response Relationship, Drug
MH  - Half-Life
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Muscarinic Antagonists/administration & dosage/*adverse effects/*pharmacokinetics
MH  - Single-Blind Method
MH  - Tropanes/administration & dosage/*adverse effects/*pharmacokinetics
EDAT- 2009/07/31 09:00
MHDA- 2009/08/21 09:00
CRDT- 2009/07/31 09:00
PHST- 2009/07/31 09:00 [entrez]
PHST- 2009/07/31 09:00 [pubmed]
PHST- 2009/08/21 09:00 [medline]
AID - 6327 [pii]
AID - 10.5414/cpp47460 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2009 Jul;47(7):460-8. doi: 10.5414/cpp47460.