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Identification
NameAclidinium
Accession NumberDB08897
TypeSmall Molecule
GroupsApproved
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.

Structure
Thumb
Synonyms
Aclidinium
External Identifiers
  • LAS-34273
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tudorza Genuairpowder (metered dose)400 mcginhalationAstrazeneca Canada Inc2013-09-13Not applicableCanada
Tudorza Pressairinhalant400 ug/1respiratory (inhalation)Astra Zeneca Pharmaceuticals Lp2015-07-01Not applicableUs
Tudorza Pressairinhalant400 ug/1respiratory (inhalation)Forest Laboratories, Inc.2012-07-23Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
Bretaris GenuairNot Available
Eklira Genuair Not Available
Brand mixtures
NameLabellerIngredients
Duaklir GenuairAstrazeneca Canada Inc
Salts
Name/CASStructureProperties
Aclidinium Bromide
320345-99-1
Thumb
  • InChI Key: XLAKJQPTOJHYDR-QTQXQZBYSA-M
  • Monoisotopic Mass: 563.07996248
  • Average Mass: 564.555
DBSALT000003
Categories
UNIIK17VY42F6C
CAS number727649-81-2
WeightAverage: 484.651
Monoisotopic: 484.161624833
Chemical FormulaC26H30NO4S2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinuclidines. These are compounds containing a 1-azabicyclo[2.2.2]octane moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinuclidines
Sub ClassNot Available
Direct ParentQuinuclidines
Alternative Parents
Substituents
  • Quinuclidine
  • Phenol ether
  • Alkyl aryl ether
  • Benzenoid
  • Piperidine
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Thiophene
  • Tertiary alcohol
  • Quaternary ammonium salt
  • Carboxylic acid ester
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Organic cation
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationAclidinium 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.
PharmacodynamicsAclidinium does not prolong the QTc interval or have significant effects on cardiac rhythm.
Mechanism of actionAclidinium 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.
Related Articles
AbsorptionBioavailability, 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 bindingNot 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 eliminationIntravenously 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 lifePlasma 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%)

ToxicityMost common adverse reactions (≥3% incidence and greater than placebo) are headache, nasopharyngitis and cough.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9907
Blood Brain Barrier+0.8883
Caco-2 permeable-0.6509
P-glycoprotein substrateSubstrate0.7017
P-glycoprotein inhibitor INon-inhibitor0.8103
P-glycoprotein inhibitor IINon-inhibitor0.6449
Renal organic cation transporterInhibitor0.6092
CYP450 2C9 substrateNon-substrate0.7784
CYP450 2D6 substrateNon-substrate0.809
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.8536
CYP450 2C9 inhibitorNon-inhibitor0.8817
CYP450 2D6 inhibitorNon-inhibitor0.5813
CYP450 2C19 inhibitorNon-inhibitor0.8022
CYP450 3A4 inhibitorNon-inhibitor0.7154
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.808
Ames testNon AMES toxic0.7753
CarcinogenicityNon-carcinogens0.9292
BiodegradationReady biodegradable0.6794
Rat acute toxicity2.6182 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7765
hERG inhibition (predictor II)Non-inhibitor0.6484
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Powder (metered dose)inhalation
Powder (metered dose)inhalation400 mcg
Inhalantrespiratory (inhalation)400 ug/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5840279 No1996-06-212016-06-21Us
US6071498 No1996-06-212016-06-21Us
US6681768 No2002-08-072022-08-07Us
US6750226 No2000-09-052020-09-05Us
US7078412 No2000-07-162020-07-16Us
US8051851 No2007-04-222027-04-22Us
US9056100 No2000-07-072020-07-07Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityVery slightly soluble FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00152 mg/mLALOGPS
logP3.07ALOGPS
logP0.45ChemAxon
logS-5.5ALOGPS
pKa (Strongest Acidic)10.35ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area55.76 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity141.33 m3·mol-1ChemAxon
Polarizability52.09 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesR03AL05R03BB05
AHFS Codes
  • 12:08.08
PDB EntriesNot Available
FDA labelDownload (1.25 MB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AmitriptylineAclidinium may increase the anticholinergic activities of Amitriptyline.
AmoxapineAclidinium may increase the anticholinergic activities of Amoxapine.
AtropineAclidinium may increase the anticholinergic activities of Atropine.
AzelastineAclidinium may increase the anticholinergic activities of Azelastine.
BenzatropineAclidinium may increase the anticholinergic activities of Benzatropine.
Botulinum Toxin Type AAclidinium may increase the anticholinergic activities of Botulinum Toxin Type A.
Botulinum Toxin Type BAclidinium may increase the anticholinergic activities of Botulinum Toxin Type B.
BrompheniramineAclidinium may increase the anticholinergic activities of Brompheniramine.
CarbinoxamineAclidinium may increase the anticholinergic activities of Carbinoxamine.
CetirizineAclidinium may increase the anticholinergic activities of Cetirizine.
ChlorphenamineAclidinium may increase the anticholinergic activities of Chlorphenamine.
ChlorpromazineAclidinium may increase the anticholinergic activities of Chlorpromazine.
Cimetropium BromideAclidinium may increase the anticholinergic activities of Cimetropium Bromide.
ClemastineAclidinium may increase the anticholinergic activities of Clemastine.
ClomipramineAclidinium may increase the anticholinergic activities of Clomipramine.
ClozapineAclidinium may increase the anticholinergic activities of Clozapine.
CyclizineAclidinium may increase the anticholinergic activities of Cyclizine.
CyclobenzaprineAclidinium may increase the anticholinergic activities of Cyclobenzaprine.
CyclopentolateAclidinium may increase the anticholinergic activities of Cyclopentolate.
CyproheptadineAclidinium may increase the anticholinergic activities of Cyproheptadine.
DarifenacinAclidinium may increase the anticholinergic activities of Darifenacin.
DesipramineAclidinium may increase the anticholinergic activities of Desipramine.
DesloratadineAclidinium may increase the anticholinergic activities of Desloratadine.
Dexchlorpheniramine maleateAclidinium may increase the anticholinergic activities of Dexchlorpheniramine maleate.
DicyclomineAclidinium may increase the anticholinergic activities of Dicyclomine.
DimenhydrinateAclidinium may increase the anticholinergic activities of Dimenhydrinate.
DiphenhydramineAclidinium may increase the anticholinergic activities of Diphenhydramine.
DisopyramideAclidinium may increase the anticholinergic activities of Disopyramide.
DoxepinAclidinium may increase the anticholinergic activities of Doxepin.
DoxylamineAclidinium may increase the anticholinergic activities of Doxylamine.
DronabinolAclidinium may increase the tachycardic activities of Dronabinol.
DroperidolAclidinium may increase the anticholinergic activities of Droperidol.
EluxadolineAclidinium may increase the activities of Eluxadoline.
FesoterodineAclidinium may increase the anticholinergic activities of Fesoterodine.
FexofenadineAclidinium may increase the anticholinergic activities of Fexofenadine.
FlavoxateAclidinium may increase the anticholinergic activities of Flavoxate.
FlupentixolAclidinium may increase the anticholinergic activities of Flupentixol.
FluphenazineAclidinium may increase the anticholinergic activities of Fluphenazine.
Glucagon recombinantThe risk or severity of adverse effects can be increased when Aclidinium is combined with Glucagon recombinant.
GlycopyrroniumAclidinium may increase the anticholinergic activities of Glycopyrrolate.
HaloperidolAclidinium may increase the anticholinergic activities of Haloperidol.
HomatropineAclidinium may increase the anticholinergic activities of Homatropine.
HydroxyzineAclidinium may increase the anticholinergic activities of Hydroxyzine.
HyoscyamineAclidinium may increase the anticholinergic activities of Hyoscyamine.
ImipramineAclidinium may increase the anticholinergic activities of Imipramine.
Ipratropium bromideAclidinium may increase the anticholinergic activities of Ipratropium bromide.
IsocarboxazidAclidinium may increase the anticholinergic activities of Isocarboxazid.
ItoprideThe therapeutic efficacy of Itopride can be decreased when used in combination with Aclidinium.
LevocabastineAclidinium may increase the anticholinergic activities of Levocabastine.
LevocetirizineAclidinium may increase the anticholinergic activities of Levocetirizine.
LoratadineAclidinium may increase the anticholinergic activities of Loratadine.
LoxapineAclidinium may increase the anticholinergic activities of Loxapine.
MaprotilineAclidinium may increase the anticholinergic activities of Maprotiline.
MeclizineAclidinium may increase the anticholinergic activities of Meclizine.
MepenzolateAclidinium may increase the anticholinergic activities of Mepenzolate.
MethotrimeprazineAclidinium may increase the anticholinergic activities of Methotrimeprazine.
MethscopolamineAclidinium may increase the anticholinergic activities of Methscopolamine.
MianserinMianserin may increase the anticholinergic activities of Aclidinium.
MirabegronThe risk or severity of adverse effects can be increased when Aclidinium is combined with Mirabegron.
MoclobemideAclidinium may increase the anticholinergic activities of Moclobemide.
MorphineThe risk or severity of adverse effects can be increased when Aclidinium is combined with Morphine.
NortriptylineAclidinium may increase the anticholinergic activities of Nortriptyline.
OlanzapineAclidinium may increase the anticholinergic activities of Olanzapine.
OlopatadineAclidinium may increase the anticholinergic activities of Olopatadine.
OrphenadrineAclidinium may increase the anticholinergic activities of Orphenadrine.
OxybutyninAclidinium may increase the anticholinergic activities of Oxybutynin.
PerphenazineAclidinium may increase the anticholinergic activities of Perphenazine.
PhenelzineAclidinium may increase the anticholinergic activities of Phenelzine.
PimozideAclidinium may increase the anticholinergic activities of Pimozide.
PizotifenAclidinium may increase the anticholinergic activities of Pizotifen.
Potassium ChlorideAclidinium may increase the ulcerogenic activities of Potassium Chloride.
PramlintidePramlintide may increase the anticholinergic activities of Aclidinium.
ProchlorperazineAclidinium may increase the anticholinergic activities of Prochlorperazine.
ProcyclidineAclidinium may increase the anticholinergic activities of Procyclidine.
PromazineAclidinium may increase the anticholinergic activities of Promazine.
PromethazineAclidinium may increase the anticholinergic activities of Promethazine.
PropanthelineAclidinium may increase the anticholinergic activities of Propantheline.
ProtriptylineAclidinium may increase the anticholinergic activities of Protriptyline.
QuetiapineAclidinium may increase the anticholinergic activities of Quetiapine.
RamosetronAclidinium may increase the activities of Ramosetron.
RisperidoneAclidinium may increase the anticholinergic activities of Risperidone.
ScopolamineAclidinium may increase the anticholinergic activities of Scopolamine.
Scopolamine butylbromideAclidinium may increase the anticholinergic activities of Scopolamine butylbromide.
SecretinThe therapeutic efficacy of Secretin can be decreased when used in combination with Aclidinium.
SolifenacinAclidinium may increase the anticholinergic activities of Solifenacin.
SulpirideThe therapeutic efficacy of Sulpiride can be decreased when used in combination with Aclidinium.
TacrineThe therapeutic efficacy of Aclidinium can be decreased when used in combination with Tacrine.
ThioridazineAclidinium may increase the anticholinergic activities of Thioridazine.
ThiothixeneAclidinium may increase the anticholinergic activities of Thiothixene.
TiotropiumAclidinium may increase the anticholinergic activities of Tiotropium.
TolterodineAclidinium may increase the anticholinergic activities of Tolterodine.
TopiramateThe risk or severity of adverse effects can be increased when Aclidinium is combined with Topiramate.
TranylcypromineAclidinium may increase the anticholinergic activities of Tranylcypromine.
TrichlormethiazideThe serum concentration of Trichlormethiazide can be increased when it is combined with Aclidinium.
TrifluoperazineAclidinium may increase the anticholinergic activities of Trifluoperazine.
TrihexyphenidylAclidinium may increase the anticholinergic activities of Trihexyphenidyl.
TrimethobenzamideAclidinium may increase the anticholinergic activities of Trimethobenzamide.
TrimipramineAclidinium may increase the anticholinergic activities of Trimipramine.
TriprolidineAclidinium may increase the anticholinergic activities of Triprolidine.
TrospiumAclidinium may increase the anticholinergic activities of Trospium.
UmeclidiniumUmeclidinium may increase the anticholinergic activities of Aclidinium.
ZuclopenthixolAclidinium may increase the anticholinergic activities of Zuclopenthixol.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
Kind
Protein
Organism
Human
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 action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then trigge...
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
Kind
Protein
Organism
Human
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
Kind
Protein
Organism
Human
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 action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:
CHRM4
Uniprot ID:
P08173
Molecular Weight:
53048.65 Da
Kind
Protein
Organism
Human
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM5
Uniprot ID:
P08912
Molecular Weight:
60073.205 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
yes
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
Molecular Weight:
68417.575 Da
References
  1. 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 ]
Comments
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Drug created on June 04, 2013 17:58 / Updated on July 27, 2016 01:58