Identification

Name
Vilanterol
Accession Number
DB09082  (DB06577)
Type
Small Molecule
Groups
Approved
Description

Vilanterol is a selective long-acting beta2-adrenergic agonist (LABA) with inherent 24-hour activity for once daily treatment of COPD and asthma. Its pharmacological effect is attributable to stimulation of intracellular adenylyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increases in cyclic AMP are associated with relaxation of bronchial smooth muscle and inhibition of release of hypersensitivity mediators from mast cells in the lungs.

Vilanterol is approved for use in several combination products such as with fluticasone furoate under the tradename Breo Ellipta and in combination with umeclidinium bromide as Anoro Ellipta. Approved by the FDA in 2013, use of Breo Ellipta is indicated for the long-term, once-daily maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and emphysema. It is also indicated for once-daily maintenance treatment of asthma in patients aged 18 or older with reversible obstructive airways disease.

Structure
Thumb
Synonyms
  • 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol
  • vilantérol
External IDs
GW 642444M / GW 642444X / GW-642444 / GW-642444M / GW-642444X / GW642444 / GW642444M / GW642444X
Product Ingredients
IngredientUNIICASInChI Key
Vilanterol Trifenatate40AHO2C6DG503070-58-4KLOLZALDXGTNQE-JIDHJSLPSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AnoroVilanterol Trifenatate (22 micrograms) + Umeclidinium bromide (55 micrograms)Powder, meteredRespiratory (inhalation)Glaxo Group Limited2014-05-08Not applicableEu
AnoroVilanterol Trifenatate (22 micrograms) + Umeclidinium bromide (55 micrograms)Powder, meteredRespiratory (inhalation)Glaxo Group Limited2014-05-08Not applicableEu
AnoroVilanterol Trifenatate (22 micrograms) + Umeclidinium bromide (55 micrograms)Powder, meteredRespiratory (inhalation)Glaxo Group Limited2014-05-08Not applicableEu
Anoro ElliptaVilanterol Trifenatate (25 ug/1) + Umeclidinium bromide (62.5 ug/1)PowderRespiratory (inhalation)Glaxosmithkline Inc2014-01-31Not applicableUs
Anoro ElliptaVilanterol (25 mcg) + Umeclidinium (62.5 mcg)PowderRespiratory (inhalation)Glaxosmithkline Inc2014-03-14Not applicableCanada
Breo ElliptaVilanterol (25 mcg) + Fluticasone furoate (100 mcg)PowderRespiratory (inhalation)Glaxosmithkline Inc2013-11-29Not applicableCanada
Breo ElliptaVilanterol Trifenatate (25 ug/1) + Fluticasone furoate (200 ug/1)PowderRespiratory (inhalation)Glaxosmithkline Inc2015-04-30Not applicableUs
Breo ElliptaVilanterol Trifenatate (25 ug/1) + Fluticasone furoate (200 ug/1)PowderRespiratory (inhalation)Glaxo Operations UK Ltd2015-04-302018-01-08Us
Breo ElliptaVilanterol Trifenatate (25 ug/1) + Fluticasone furoate (100 ug/1)PowderRespiratory (inhalation)Glaxo Operations UK Ltd2013-08-262018-01-08Us
Breo ElliptaVilanterol Trifenatate (25 ug/1) + Fluticasone furoate (200 ug/1)PowderRespiratory (inhalation)A-S Medication Solutions2015-04-30Not applicableUs
Categories
UNII
028LZY775B
CAS number
503068-34-6
Weight
Average: 486.43
Monoisotopic: 485.1735786
Chemical Formula
C24H33Cl2NO5
InChI Key
DAFYYTQWSAWIGS-DEOSSOPVSA-N
InChI
InChI=1S/C24H33Cl2NO5/c25-21-6-5-7-22(26)20(21)17-32-13-12-31-11-4-2-1-3-10-27-15-24(30)18-8-9-23(29)19(14-18)16-28/h5-9,14,24,27-30H,1-4,10-13,15-17H2/t24-/m0/s1
IUPAC Name
4-[(1R)-2-[(6-{2-[(2,6-dichlorophenyl)methoxy]ethoxy}hexyl)amino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol
SMILES
[H][C@](O)(CNCCCCCCOCCOCC1=C(Cl)C=CC=C1Cl)C1=CC(CO)=C(O)C=C1

Pharmacology

Indication

Vilanterol is approved for use in several combination products such as with fluticasone furoate under the tradename Breo Ellipta and in combination with umeclidinium bromide as Anoro Ellipta. Approved by the FDA in 2013, use of Breo Ellipta is indicated for the long-term, once-daily maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and emphysema. It is also indicated for once-daily maintenance treatment of asthma in patients aged 18 or older with reversible obstructive airways disease.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Vilanterol is a selective long-acting beta2-adrenergic agonist. Its pharmacological effect is attributable to stimulation of intracellular adenylyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increases in cyclic AMP are associated with relaxation of bronchial smooth muscle and inhibition of release of hypersensitivity mediators from mast cells in the lungs.

TargetActionsOrganism
ABeta-2 adrenergic receptor
agonist
Human
Absorption

Peak plasma concentrations are achieved within 10 minutes of inhalation. Absolute bioavailability was found to be 27.3% when administered by inhalation, whereas oral bioavailability was found to be less than 2% due to extensive first-pass metabolism. Systemic exposure is 24% higher in patients with COPD as compared to healthy subjects.

Volume of distribution

Following IV administration to healthy subjects, the mean volume of distribution at steady state was 661 L.

Protein binding

Binding to plasma protein was 93.9%.

Metabolism

Vilanterol is principally metabolized by cytochrome p450 3A4 (CYP3A4) to a range of metabolites with significantly reduced beta1- and beta2-agonist activity. The major route of metabolism was via O-dealkylation, with up to 78% of the recovered dose eliminated as O-dealkylated metabolites while N-Dealkylation and C-dealkylation were minor pathways, representing 5% of the recovered dose.

Route of elimination

Following oral administration, vilanterol is eliminated mainly by metabolism by CYP3A4 followed by excretion of metabolites in urine (70%) and feces (30%).

Half life

21.3 hr

Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Vilanterol can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Vilanterol.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Vilanterol.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Vilanterol.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Vilanterol.
5-androstenedioneThe metabolism of Vilanterol can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Vilanterol can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Vilanterol.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Vilanterol is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbacavirAbacavir may decrease the excretion rate of Vilanterol which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Harrell AW, Siederer SK, Bal J, Patel NH, Young GC, Felgate CC, Pearce SJ, Roberts AD, Beaumont C, Emmons AJ, Pereira AI, Kempsford RD: Metabolism and disposition of vilanterol, a long-acting beta(2)-adrenoceptor agonist for inhalation use in humans. Drug Metab Dispos. 2013 Jan;41(1):89-100. doi: 10.1124/dmd.112.048603. Epub 2012 Oct 4. [PubMed:23043183]
  2. Spyratos D, Sichletidis L: Umeclidinium bromide/vilanterol combination in the treatment of chronic obstructive pulmonary disease: a review. Ther Clin Risk Manag. 2015 Mar 25;11:481-7. doi: 10.2147/TCRM.S67491. eCollection 2015. [PubMed:25848294]
External Links
KEGG Drug
D10501
PubChem Compound
10184665
PubChem Substance
347827825
ChemSpider
8360167
BindingDB
50416060
ChEBI
75037
ChEMBL
CHEMBL1198857
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vilanterol
ATC Codes
R03AK10 — Vilanterol and fluticasone furoateR03AL03 — Vilanterol and umeclidinium bromide
FDA label
Download (12.2 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAsthma Bronchial1
1CompletedNot AvailableHealthy Volunteers / Pulmonary Disease, Chronic Obstructive1
1CompletedBasic ScienceAsthma Bronchial1
1CompletedOtherAsthma Bronchial1
1CompletedOtherPulmonary Disease, Chronic Obstructive1
1CompletedPreventionHealthy Volunteers / Pulmonary Disease, Chronic Obstructive1
1CompletedTreatmentAsthma Bronchial / Healthy Volunteers2
1CompletedTreatmentAsthma Bronchial / Pulmonary Disease, Chronic Obstructive2
1CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Disease, Chronic Obstructive1
1CompletedTreatmentHealthy Volunteers / Pulmonary Disease, Chronic Obstructive2
1CompletedTreatmentPulmonary Disease, Chronic Obstructive3
1, 2RecruitingTreatmentAsthma Bronchial / Chronic Obstructive Pulmonary Disease (COPD)1
2CompletedTreatmentAsthma Bronchial6
2CompletedTreatmentAsthma Bronchial / Pulmonary Disease, Chronic Obstructive2
2CompletedTreatmentPulmonary Disease, Chronic Obstructive7
2RecruitingDiagnosticChronic Obstructive Pulmonary Disease (COPD)1
2RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)1
3CompletedOtherPulmonary Disease, Chronic Obstructive1
3CompletedTreatmentAsthma Bronchial5
3CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)4
3CompletedTreatmentPulmonary Disease, Chronic Obstructive14
4CompletedTreatmentAsthma Bronchial1
4CompletedTreatmentPulmonary Disease, Chronic Obstructive1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Powder, meteredRespiratory (inhalation)
PowderRespiratory (inhalation)
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5873360Yes1999-02-232016-08-23Us
US7101866No2006-09-052021-08-03Us
US7439393No2008-10-212022-09-11Us
US6759398No2004-07-062021-08-03Us
USRE44874No2014-04-292023-03-23Us
US6537983No2003-03-252021-08-03Us
US8511304No2013-08-202027-06-14Us
US7629335No2009-12-082021-08-03Us
US8161968No2012-04-242028-02-05Us
US8746242No2014-06-102030-10-11Us
US8113199No2012-02-142027-10-23Us
US7776895No2010-08-172022-09-11Us
US8534281No2013-09-172029-08-10Us
US6878698No2005-04-122021-08-03Us
US8309572No2012-11-132025-04-27Us
US8183257No2012-05-222025-07-27Us
US7488827No2009-02-102025-04-27Us
US7498440No2009-03-032025-04-27Us
US9333310No2016-05-102027-10-02Us
US9750726No2017-09-052030-11-29Us
US9750762No2017-09-052030-11-29Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00118 mg/mLALOGPS
logP3.39ALOGPS
logP3.6ChemAxon
logS-5.6ALOGPS
pKa (Strongest Acidic)10.12ChemAxon
pKa (Strongest Basic)9.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area91.18 Å2ChemAxon
Rotatable Bond Count16ChemAxon
Refractivity129.09 m3·mol-1ChemAxon
Polarizability53.12 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzylethers
Direct Parent
Benzylethers
Alternative Parents
Dichlorobenzenes / Benzyl alcohols / Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Aryl chlorides / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Dialkyl ethers / Primary alcohols
show 4 more
Substituents
Benzylether / Benzyl alcohol / 1,3-dichlorobenzene / 1-hydroxy-2-unsubstituted benzenoid / Aralkylamine / Chlorobenzene / Phenol / Halobenzene / Aryl chloride / Aryl halide
show 19 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
phenols, benzyl alcohols, secondary amino compound, ether, dichlorobenzene (CHEBI:75037)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Drug created on August 31, 2015 11:12 / Updated on November 02, 2018 08:46