Aclidinium
Identification
- Summary
Aclidinium is an inhaled long-acting anticholinergic used as a maintenance bronchodilator in patients with chronic obstructive pulmonary disease (COPD).
- Brand Names
- Bretaris Genuair, Duaklir, Duaklir Genuair, Eklira Genuair, Tudorza, Tudorza Genuair
- Generic Name
- Aclidinium
- DrugBank Accession Number
- DB08897
- Background
Aclidinium is an anticholinergic for the long-term management of chronic obstructive pulmonary disease (COPD). It has a much higher propensity to bind to muscarinic receptors than nicotinic receptors. FDA approved on July 24, 2012.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Aclidinium (DB08897)
- Weight
- Average: 484.651
Monoisotopic: 484.161624833 - Chemical Formula
- C26H30NO4S2
- Synonyms
- Aclidinio
- External IDs
- LAS-34273
Pharmacology
- Indication
Aclidinium bromide inhalation powder is indicated for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Aclidinium does not prolong the QTc interval or have significant effects on cardiac rhythm.
- Mechanism of action
Aclidinium is a long-acting, competitive, and reversible anticholinergic drug that is specific for the acetylcholine muscarinic receptors. It binds to all 5 muscarinic receptor subtypes to a similar affinity. Aclidinium's effects on the airways are mediated through the M3 receptor at the smooth muscle to cause bronchodilation. Prevention of acetylcholine-induced bronchoconstriction effects was dose-dependent and lasted longer than 24 hours.
Target Actions Organism AMuscarinic acetylcholine receptor M1 antagonistHumans AMuscarinic acetylcholine receptor M2 antagonistHumans AMuscarinic acetylcholine receptor M3 antagonistHumans AMuscarinic acetylcholine receptor M4 antagonistHumans AMuscarinic acetylcholine receptor M5 antagonistHumans - Absorption
Bioavailability, healthy subjects = 6%; T max, healthy subjects = 10 minutes; Time to steady state, healthy subjects = 2 days;
- Volume of distribution
Following IV administration, the volume of distribution is 300 L
- Protein binding
Not Available
- Metabolism
The major route of metabolism of aclidinium bromide is hydrolysis, which occurs both chemically and enzymatically by esterases in the plasma. Aclidinium bromide is rapidly and extensively hydrolyzed to its alcohol and dithienylglycolic acid derivatives, neither of which binds to muscarinic receptors and are pharmacologically inactive.
- Route of elimination
Intravenously administered radiolabelled aclidinium bromide was administered to healthy volunteers and was extensively metabolized with 1% excreted as unchanged aclidinium. Approximately 54% to 65% of the radioactivity was excreted in urine and 20% to 33% of the dose was excreted in feces. The combined results indicated that almost the entire aclidinium bromide dose was eliminated by hydrolysis. After dry powder inhalation, urinary excretion of aclidinium is about 0.09% of the dose.
- Half-life
Plasma half-life = 2.4 minutes (indicating that aclidinium is very rapidly hydrolyzed in plasma into its two inactive metabolites and has a low chance of causing systemic side effects). Effective half-life = 5-8 hours.
- Clearance
Total clearance, IV dose, young healthy subjects = 170 L/h (inter-individual variability of 36%)
- Adverse Effects
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Most common adverse reactions (≥3% incidence and greater than placebo) are headache, nasopharyngitis and cough.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine 1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium. Abacavir Abacavir may decrease the excretion rate of Aclidinium which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acetazolamide Acetazolamide may increase the central nervous system depressant (CNS depressant) activities of Aclidinium. Acetophenazine Acetophenazine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acrivastine Aclidinium may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Aclidinium which could result in a higher serum level. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Aclidinium bromide UQW7UF9N91 320345-99-1 XLAKJQPTOJHYDR-QTQXQZBYSA-M - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Bretaris Genuair 322 μg Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU 
Bretaris Genuair 322 μg Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU Bretaris Genuair 322 μg Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU Eklira Genuair 322 μg Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU Eklira Genuair 322 μg Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU Eklira Genuair 322 μg Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU Tudorza Genuair Powder, metered 400 mcg / act Respiratory (inhalation) Astra Zeneca 2013-09-13 Not applicable Canada 
Tudorza Pressair Powder, metered 400 ug/1 Respiratory (inhalation) AstraZeneca Pharmaceuticals LP 2015-07-01 Not applicable US 
Tudorza Pressair Inhalant 400 ug/1 Respiratory (inhalation) Allergan 2012-07-23 2017-10-20 US Tudorza Pressair Powder, metered 400 ug/1 Respiratory (inhalation) Circassia Pharmaceuticals Inc. 2019-07-01 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Brimica Genuair Aclidinium bromide (340 μg) + Formoterol fumarate (12 μg) Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU Brimica Genuair Aclidinium bromide (340 μg) + Formoterol fumarate (12 μg) Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU Brimica Genuair Aclidinium bromide (340 μg) + Formoterol fumarate (12 μg) Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU Duaklir Genuair Aclidinium bromide (340 μg) + Formoterol fumarate (12 μg) Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU Duaklir Genuair Aclidinium bromide (340 μg) + Formoterol fumarate (12 μg) Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU Duaklir Genuair Aclidinium bromide (400 mcg / act) + Formoterol fumarate (12 mcg / act) Powder, metered Respiratory (inhalation) Astra Zeneca 2015-07-09 Not applicable Canada Duaklir Genuair Aclidinium bromide (340 μg) + Formoterol fumarate (12 μg) Respiratory (inhalation) Astra Zeneca Ab 2016-09-08 Not applicable EU DUAKLIR GENUAIR INHALATION POWDER 340/12 MICROGRAM/DOSE Aclidinium (343 mcg) + Formoterol fumarate (12 mcg) Powder, metered Respiratory (inhalation) ASTRAZENECA SINGAPORE PTE LTD 2017-05-03 Not applicable Singapore Duaklir Pressair Aclidinium bromide (400 ug/1) + Formoterol fumarate (12 ug/1) Powder, metered Respiratory (inhalation) Circassia Pharmaceuticals Inc. 2019-10-11 Not applicable US DUAKLIR®GENUAIR®340/12MCG/DOSIS. Aclidinium (400 mcg) + Formoterol fumarate (12 mcg) Powder Respiratory (inhalation) ASTRAZENECA COLOMBIA S.A.S 2017-12-11 Not applicable Colombia 
Categories
- ATC Codes
- R03BB05 — Aclidinium bromide
- R03BB — Anticholinergics
- R03B — OTHER DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES, INHALANTS
- R03 — DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
- R — RESPIRATORY SYSTEM
- Drug Categories
- Adrenergics, Inhalants
- Agents producing tachycardia
- Agents to Treat Airway Disease
- Alkaloids
- Anticholinergic Agents
- Antimuscarinics Antispasmodics
- Aza Compounds
- Azabicyclo Compounds
- Cholinesterase substrates
- Drugs for Obstructive Airway Diseases
- Drugs that are Mainly Renally Excreted
- Muscarinic Antagonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as quinuclidines. These are compounds containing a 1-azabicyclo[2.2.2]octane moiety.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Quinuclidines
- Sub Class
- Not Available
- Direct Parent
- Quinuclidines
- Alternative Parents
- Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Piperidines / Thiophenes / Tetraalkylammonium salts / Tertiary alcohols / Heteroaromatic compounds / Carboxylic acid esters / Azacyclic compounds show 9 more
- Substituents
- Alcohol / Alkyl aryl ether / Amine / Aromatic alcohol / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester show 21 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- aromatic ether, carboxylic ester, quaternary ammonium ion, thiophenes (CHEBI:65346)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- K17VY42F6C
- CAS number
- 727649-81-2
- InChI Key
- ASMXXROZKSBQIH-VITNCHFBSA-N
- InChI
- InChI=1S/C26H30NO4S2/c28-25(26(29,23-9-4-17-32-23)24-10-5-18-33-24)31-22-19-27(14-11-20(22)12-15-27)13-6-16-30-21-7-2-1-3-8-21/h1-5,7-10,17-18,20,22,29H,6,11-16,19H2/q+1/t20?,22-,27?/m0/s1
- IUPAC Name
- (3R)-3-{[2-hydroxy-2,2-bis(thiophen-2-yl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azabicyclo[2.2.2]octan-1-ium
- SMILES
- OC(C(=O)O[C@H]1C[N+]2(CCCOC3=CC=CC=C3)CCC1CC2)(C1=CC=CS1)C1=CC=CS1
References
- General References
- Reid DJ, Pham NT: Emerging Therapeutic Options for the Management of COPD. Clin Med Insights Circ Respir Pulm Med. 2013 Apr 9;7:7-15. doi: 10.4137/CCRPM.S8140. Print 2013. [Article]
- Cazzola M, Page CP, Matera MG: Aclidinium bromide for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2013 Jun;14(9):1205-14. doi: 10.1517/14656566.2013.789021. Epub 2013 Apr 9. [Article]
- Jones P: Aclidinium bromide twice daily for the treatment of chronic obstructive pulmonary disease: a review. Adv Ther. 2013 Apr;30(4):354-68. doi: 10.1007/s12325-013-0019-2. Epub 2013 Apr 2. [Article]
- Alberti J, Martinet A, Sentellas S, Salva M: Identification of the human enzymes responsible for the enzymatic hydrolysis of aclidinium bromide. Drug Metab Dispos. 2010 Jul;38(7):1202-10. doi: 10.1124/dmd.109.031724. Epub 2010 Mar 23. [Article]
- External Links
- KEGG Drug
- D08837
- PubChem Compound
- 11434515
- PubChem Substance
- 175427140
- ChemSpider
- 9609381
- BindingDB
- 50296331
- 1303098
- ChEBI
- 65346
- ChEMBL
- CHEMBL1194325
- ZINC
- ZINC000030691727
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Aclidinium_bromide
- FDA label
- Download (1.25 MB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Basic Science Chronic Obstructive Pulmonary Disease (COPD) 1 4 Completed Treatment Chronic Obstructive Pulmonary Disease (COPD) 6 4 Completed Treatment Chronic Obstructive Pulmonary Disease (COPD) / Moderate to Very Severe COPD 1 4 Recruiting Other Chronic Obstructive Pulmonary Disease (COPD) 1 4 Recruiting Treatment Chronic Obstructive Pulmonary Disease (COPD) 1 4 Withdrawn Treatment Chronic Obstructive Pulmonary Disease (COPD) 1 3 Completed Not Available Chronic Obstructive Pulmonary Disease (COPD) 1 3 Completed Treatment Chronic Obstructive Pulmonary Disease (COPD) 17 3 Completed Treatment Smoking 1 3 Recruiting Treatment Chronic Obstructive Pulmonary Disease (COPD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Aerosol, powder Respiratory (inhalation) 322 mg Aerosol, powder Respiratory (inhalation) Powder, metered Respiratory (inhalation) 343 mcg Powder, metered Respiratory (inhalation) Powder Respiratory (inhalation) Powder, metered Respiratory (inhalation) Powder, metered Respiratory (inhalation) 343 mcg Powder Respiratory (inhalation) 322 mcg Powder, metered Respiratory (inhalation) 400 mcg / act Inhalant Respiratory (inhalation) 400 ug/1 Powder, metered Respiratory (inhalation) 400 ug/1 Powder Respiratory (inhalation) Powder Respiratory (inhalation) 400 mcg/1dose - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6750226 No 2004-06-15 2020-09-05 US US7078412 No 2006-07-18 2020-07-16 US US9056100 No 2015-06-16 2020-07-07 US US6681768 No 2004-01-27 2022-08-07 US US8051851 No 2011-11-08 2027-04-22 US US6071498 No 2000-06-06 2016-06-21 US US5840279 No 1998-11-24 2016-06-21 US USRE46417 No 2017-05-30 2020-09-05 US US9333195 No 2016-05-10 2020-07-07 US US10085974 No 2018-10-02 2029-03-13 US US10034867 No 2018-07-31 2020-07-07 US US7750023 No 2010-07-06 2020-07-07 US US8129405 No 2012-03-06 2020-07-07 US US10588895 No 2020-03-17 2022-01-14 US US11000517 No 2009-03-13 2029-03-13 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Very slightly soluble FDA label - Predicted Properties
Property Value Source Water Solubility 0.00152 mg/mL ALOGPS logP 3.07 ALOGPS logP 0.45 ChemAxon logS -5.5 ALOGPS pKa (Strongest Acidic) 10.35 ChemAxon pKa (Strongest Basic) -4.8 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 55.76 Å2 ChemAxon Rotatable Bond Count 10 ChemAxon Refractivity 141.33 m3·mol-1 ChemAxon Polarizability 52.09 Å3 ChemAxon Number of Rings 5 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.9907 Blood Brain Barrier + 0.8883 Caco-2 permeable - 0.6509 P-glycoprotein substrate Substrate 0.7017 P-glycoprotein inhibitor I Non-inhibitor 0.8103 P-glycoprotein inhibitor II Non-inhibitor 0.6449 Renal organic cation transporter Inhibitor 0.6092 CYP450 2C9 substrate Non-substrate 0.7784 CYP450 2D6 substrate Non-substrate 0.809 CYP450 3A4 substrate Non-substrate 0.5 CYP450 1A2 substrate Non-inhibitor 0.8536 CYP450 2C9 inhibitor Non-inhibitor 0.8817 CYP450 2D6 inhibitor Non-inhibitor 0.5813 CYP450 2C19 inhibitor Non-inhibitor 0.8022 CYP450 3A4 inhibitor Non-inhibitor 0.7154 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.808 Ames test Non AMES toxic 0.7753 Carcinogenicity Non-carcinogens 0.9292 Biodegradation Ready biodegradable 0.6794 Rat acute toxicity 2.6182 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7765 hERG inhibition (predictor II) Non-inhibitor 0.6484
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Phosphatidylinositol phospholipase c activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM1
- Uniprot ID
- P11229
- Uniprot Name
- Muscarinic acetylcholine receptor M1
- Molecular Weight
- 51420.375 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- G-protein coupled acetylcholine receptor activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM2
- Uniprot ID
- P08172
- Uniprot Name
- Muscarinic acetylcholine receptor M2
- Molecular Weight
- 51714.605 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Receptor activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM3
- Uniprot ID
- P20309
- Uniprot Name
- Muscarinic acetylcholine receptor M3
- Molecular Weight
- 66127.445 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Guanyl-nucleotide exchange factor activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM4
- Uniprot ID
- P08173
- Uniprot Name
- Muscarinic acetylcholine receptor M4
- Molecular Weight
- 53048.65 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Phosphatidylinositol phospholipase c activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM5
- Uniprot ID
- P08912
- Uniprot Name
- Muscarinic acetylcholine receptor M5
- Molecular Weight
- 60073.205 Da
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Identical protein binding
- Specific Function
- Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
- Gene Name
- BCHE
- Uniprot ID
- P06276
- Uniprot Name
- Cholinesterase
- Molecular Weight
- 68417.575 Da
References
- Cazzola M, Page CP, Matera MG: Aclidinium bromide for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2013 Jun;14(9):1205-14. doi: 10.1517/14656566.2013.789021. Epub 2013 Apr 9. [Article]
- Alberti J, Martinet A, Sentellas S, Salva M: Identification of the human enzymes responsible for the enzymatic hydrolysis of aclidinium bromide. Drug Metab Dispos. 2010 Jul;38(7):1202-10. doi: 10.1124/dmd.109.031724. Epub 2010 Mar 23. [Article]
Drug created on June 04, 2013 23:58 / Updated on October 22, 2021 23:18