Aclidinium

Identification

Name

Aclidinium

Accession Number

DB08897

Description

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

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Aclidinium (DB08897)

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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.

Associated Conditions

• Chronic Obstructive Pulmonary Disease (COPD)

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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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	antagonist	Humans
AMuscarinic acetylcholine receptor M2	antagonist	Humans
AMuscarinic acetylcholine receptor M3	antagonist	Humans
AMuscarinic acetylcholine receptor M4	antagonist	Humans
AMuscarinic acetylcholine receptor M5	antagonist	Humans

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

Learn about our commercial Adverse Effects data.

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Toxicity

Most common adverse reactions (≥3% incidence and greater than placebo) are headache, nasopharyngitis and cough.

Affected organisms

• Humans and other mammals

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abacavir	Abacavir may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Acarbose	Acarbose 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.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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Action
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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Food Interactions

No interactions found.

Products

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
Unlock Additional Data
Bretaris Genuair		322 μg	Respiratory (inhalation)	Astra Zeneca Ab	2012-07-20	Not applicable
Bretaris Genuair		322 μg	Respiratory (inhalation)	Astra Zeneca Ab	2012-07-20	Not applicable
Bretaris Genuair		322 μg	Respiratory (inhalation)	Astra Zeneca Ab	2012-07-20	Not applicable
Duaklir Genuair			Respiratory (inhalation)	Astra Zeneca Ab	2014-11-18	Not applicable
Duaklir Genuair			Respiratory (inhalation)	Astra Zeneca Ab	2014-11-18	Not applicable
Duaklir Genuair			Respiratory (inhalation)	Astra Zeneca Ab	2014-11-18	Not applicable
Eklira Genuair		322 μg	Respiratory (inhalation)	Astra Zeneca Ab	2012-07-20	Not applicable
Eklira Genuair		322 μg	Respiratory (inhalation)	Astra Zeneca Ab	2012-07-20	Not applicable
Eklira Genuair		322 μg	Respiratory (inhalation)	Astra Zeneca Ab	2012-07-20	Not applicable
Tudorza Genuair	Powder, metered		Respiratory (inhalation)	Astra Zeneca	2013-09-13	Not applicable

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Duaklir Genuair	Aclidinium bromide (400 mcg) + Formoterol fumarate (12 mcg)	Powder, metered	Respiratory (inhalation)	Astra Zeneca	2015-07-09	Not applicable
Duaklir Pressair	Aclidinium bromide (400 ug/1) + Formoterol fumarate (12 ug/1)	Powder, metered	Respiratory (inhalation)	Circassia Pharmaceuticals Inc.	2019-10-11	Not applicable

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

R03AL05 — Formoterol and aclidinium bromide

• R03AL — Adrenergics in combination with anticholinergics incl. triple combinations with corticosteroids
• R03A — ADRENERGICS, 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 / Monocarboxylic acids and derivatives / Organopnictogen compounds / Hydrocarbon derivatives / Organic oxides / Carbonyl compounds / Organic salts / Aromatic alcohols / Amines / Organic cations

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Substituents

Alcohol / Alkyl aryl ether / Amine / Aromatic alcohol / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Ether / Heteroaromatic compound / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Monocyclic benzene moiety / Organic cation / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organic salt / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Phenol ether / Phenoxy compound / Piperidine / Quaternary ammonium salt / Quinuclidine / Tertiary alcohol / Tetraalkylammonium salt / Thiophene

show 21 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

aromatic ether, carboxylic ester, quaternary ammonium ion, thiophenes (CHEBI:65346)

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[[email protected]]1C[N+]2(CCCOC3=CC=CC=C3)CCC1CC2)(C1=CC=CS1)C1=CC=CS1

References

General References

1. 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. [PubMed:23641160]
2. 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. [PubMed:23566013]
3. 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. [PubMed:23553509]

External Links

KEGG Drug

D08837

PubChem Compound

11434515

PubChem Substance

175427140

ChemSpider

9609381

BindingDB

50296331

RxNav

1303098

ChEBI

65346

ChEMBL

CHEMBL1194325

ZINC

ZINC000030691727

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Aclidinium_bromide

AHFS Codes

• 12:08.08 — Antimuscarinics Antispasmodics

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	Active Not Recruiting	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

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Powder	Respiratory (inhalation)	322 MICROGRAMMI
Powder	Respiratory (inhalation)	340 mcg
Powder, metered	Respiratory (inhalation)
Powder	Respiratory (inhalation)	400 mcg
Powder	Respiratory (inhalation)
Powder	Respiratory (inhalation)	322 mcg
Powder, metered	Respiratory (inhalation)
Inhalant	Respiratory (inhalation)	400 ug/1
Powder, metered	Respiratory (inhalation)	400 ug/1

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
Unlock Additional Data
US6750226	No	2004-06-15	2020-09-05
US7078412	No	2006-07-18	2020-07-16
US9056100	No	2015-06-16	2020-07-07
US6681768	No	2004-01-27	2022-08-07
US8051851	No	2011-11-08	2027-04-22
US6071498	No	2000-06-06	2016-06-21
US5840279	No	1998-11-24	2016-06-21
USRE46417	No	2017-05-30	2020-09-05
US9333195	No	2016-05-10	2020-07-07
US10085974	No	2018-10-02	2029-03-13
US10034867	No	2018-07-31	2020-07-07
US7750023	No	2010-07-06	2020-07-07
US8129405	No	2012-03-06	2020-07-07
US10588895	No	2002-01-14	2022-01-14

Additional Data Available

Filed On
Filed On
The date on which a patent was filed with the relevant government.
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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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

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Drug created on June 04, 2013 17:58 / Updated on October 27, 2020 11:13