Aclidinium bromide

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Aclidinium bromide
Aclidinium bromide.svg
Systematic (IUPAC) name
[(8R)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-8-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate bromide
Clinical data
Trade names Bretaris Genuair, Eklira Genuair, Tudorza Pressair
Licence data US FDA:link
Pregnancy cat. C (US)
Legal status -only (US)
Routes Inhalational
Identifiers
CAS number 320345-99-1 N
ATC code R03BB05
PubChem CID 11519741
ChemSpider 9694529 N
UNII UQW7UF9N91 N
KEGG D08837 YesY
ChEBI CHEBI:65344 N
ChEMBL CHEMBL551466 N
Chemical data
Formula C26H30BrNO4S2 
Mol. mass 564.555 g/mol
 N (what is this?)  (verify)

Aclidinium bromide (INN, marketed under the brand name Tudorza Pressair in the US, Eklira Genuair in the UK, and Tudorza Genuair in Canada; licensed to Menarini under the brand name Bretaris Genuair for majority of EU member states[1]) is a long-acting, inhaled muscarinic antagonist approved in the US on July 24, 2012[2] as a maintenance treatment for chronic obstructive pulmonary disease (COPD).[3]

Preclinically, aclidinium showed potent antagonism of human muscarinic receptors, with a long residence time at M3 receptors and a shorter residence time at M2 receptors, indicating the potential to provide sustained bronchodilation.[4] Aclidinium is rapidly hydrolysed in human plasma, unlike other currently available antimuscarinics including tiotropium.[4][5] This results in very low and transient systemic exposure, suggesting a reduced potential for class-related systemic side effects in the clinical setting.[4][5]

Early clinical studies in healthy subjects have confirmed the low systemic bioavailability and favourable safety profile of single and multiple doses of aclidinium.[6][7] In a subsequent Phase IIb study, which included 464 patients with moderate to severe COPD, aclidinium displayed long-lasting bronchodilatory activity and was well tolerated.[8]

Aclidinium is delivered via a novel, multidose dry powder inhaler, the Genuair inhaler.

References[edit]

  1. ^ "Almirall and Menarini sign a licence agreement and commercial alliance for Aclidinium in the majority of European member states and a number of non-EU countries" (Press release). Menarini. Retrieved 2012-03-26. 
  2. ^ "Forest Laboratories and Almirall Announce FDA Approval of Tudorza™ Pressair™ for the Long-Term Maintenance Treatment of COPD" (Press release). Forest Laboratories. Retrieved 2012-07-24. 
  3. ^ Gavaldà A, Miralpeix M, Ramos I, et al (2009). "Characterization of aclidinium bromide, a novel inhaled muscarinic antagonist, with long duration of action and a favorable pharmacological profile". J Pharmacol Exp Ther. Epub ahead of print. 
  4. ^ a b c Gavaldà A, Miralpeix M, Ramos I (2007). "Aclidinium bromide, a novel muscarinic receptor antagonist combining long residence at M3 receptors and rapid plasma clearance". Eur Respir J 30 (suppl 51): 209S–210S. 
  5. ^ a b Gavaldà A, Sentellas S, Alberti J, et al (2008). "Aclidinium bromide, a novel long-acting anticholinergic, is rapidly inactivated in plasma". Am J Respir Crit Care Med 177: A–654. 
  6. ^ Janset JM, Lamarca R, Garcia Gil E, Ferrer P. (2009). "Safety and pharmacokinetics of single doses of aclidinium bromide, a novel long-acting, inhaled antimuscarinic, in healthy subjects". Int J Clin Pharmacol Ther 47 (7): 460–468. PMID 19640353. 
  7. ^ Janset JM, Lamarca R, de Miquel G, Schrödter A, Miletzki B, Gurniak M. (2009). "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". J Clin Pharmacol. Epub ahead of print. 
  8. ^ Chanez P, Burge PS, Dahl R, et al (2009). "Aclidinium bromide provides long-acting bronchodilation in patients with COPD". Pulm Pharmacol Ther. Epub ahead of print.