Identification
- Summary
Olodaterol is a long-acting beta2-adrenergic agonist used in the management of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
- Brand Names
- Inspiolto Respimat, Stiolto, Striverdi Respimat
- Generic Name
- Olodaterol
- DrugBank Accession Number
- DB09080
- Background
Olodaterol is a novel, long-acting beta2-adrenergic agonist (LABA) that exerts its pharmacological effect by binding and activating beta2-adrenergic receptors located primarily in the lungs. Beta2-adrenergic receptors are membrane-bound receptors that are normally activated by endogenous epinephrine whose signalling, via a downstream L-type calcium channel interaction, mediates smooth muscle relaxation and bronchodilation. Activation of the receptor stimulates an associated G protein which then activates adenylate cyclase, catalyzing the formation of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA). Elevation of these two molecules induces bronchodilation by relaxation of airway smooth muscles. It is by this mechanism that olodaterol is used for the treatment of chronic obstructive pulmonary disease (COPD) and the progressive airflow obstruction that is characteristic of it. Treatment with bronchodilators helps to mitigate associated symptoms such as shortness of breath, cough, and sputum production. Single doses of olodaterol have been shown to improve forced expiratory volume in 1 sec (FEV1) for 24 h in patients with COPD, allowing once daily dosing. A once-a-day treatment with a LABA has several advantages over short-acting bronchodilators and twice-daily LABAs including improved convenience and compliance and improved airflow over a 24-hour period. Despite similarities in symptoms, olodaterol is not indicated for the treatment of acute exacerbations of COPD or for the treatment of asthma.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Olodaterol (DB09080)
- Weight
- Average: 386.448
Monoisotopic: 386.184171945 - Chemical Formula
- C21H26N2O5
- Synonyms
- Olodaterol
- External IDs
- BI 1744
- BI-1744
- BI1744
Pharmacology
- Indication
Olodaterol is indicated for use in chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. It is not indicated for the treatment of acute exacerbations of COPD or for the treatment of asthma.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to manage Chronic obstructive pulmonary disease Combination Product in combination with: Tiotropium (DB01409) •••••••••••• •••••••• Management of Chronic obstructive pulmonary disease •••••••••••• •••••••• - Contraindications & Blackbox Warnings
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Olodaterol is a potent agonist of the human beta2-adrenergic receptor in vitro, and is highly selective for this receptor, with much lower levels of activity at the b1- and b3-adrenergic receptors that are commonly expressed on cardiac smooth muscle and adipose tissue, respectively. Binding to the receptor causes smooth muscle relaxation in the lungs and bronchodilation. It has also been shown to potently reverse active bronchoconstriction.
- Mechanism of action
Olodaterol is a long-acting beta2-adrenergic agonist (LABA) that exerts its pharmacological effect by binding and activating beta2-adrenergic receptors located primarily in the lungs. Beta2-adrenergic receptors are membrane-bound receptors that are normally activated by endogenous epinephrine whose signalling, via a downstream L-type calcium channel interaction, mediates smooth muscle relaxation and bronchodilation. Activation of the receptor stimulates an associated G protein which then activates adenylate cyclase, catalyzing the formation of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA). Elevation of these two molecules induces bronchodilation by relaxation of airway smooth muscles.
Target Actions Organism ABeta-2 adrenergic receptor agonistHumans - Absorption
Olodaterol reaches maximum plasma concentrations generally within 10 to 20 minutes following drug inhalation. In healthy volunteers, the absolute bioavailability of olodaterol following inhalation was estimated to be approximately 30%, whereas the absolute bioavailability was below 1% when given as an oral solution. Thus, the systemic availability of olodaterol after inhalation is mainly determined by lung absorption, while any swallowed portion of the dose only negligibly contributes to systemic exposure.
- Volume of distribution
The volume of distribution is high (1110 L), suggesting extensive distribution into tissue.
- Protein binding
In vitro binding of olodaterol to human plasma proteins is independent of concentration and is approximately 60%.
- Metabolism
Olodaterol is substantially metabolized by direct glucuronidation and by O-demethylation at the methoxy moiety followed by conjugation. Of the six metabolites identified, only the unconjugated demethylation product binds to beta2-receptors. This metabolite, however, is not detectable in plasma after chronic inhalation of the recommended therapeutic dose. Cytochrome P450 isozymes CYP2C9 and CYP2C8, with negligible contribution of CYP3A4, are involved in the O-demethylation of olodaterol, while uridine diphosphate glycosyl transferase isoforms UGT2B7, UGT1A1, 1A7, and 1A9 were shown to be involved in the formation of olodaterol glucuronides.
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- Route of elimination
Following intravenous administration of [14C]-labeled olodaterol, 38% of the radioactive dose was recovered in the urine and 53% was recovered in feces. The amount of unchanged olodaterol recovered in the urine after intravenous administration was 19%. Following oral administration, only 9% of olodaterol and/or its metabolites was recovered in urine, while the major portion was recovered in feces (84%).
- Half-life
The terminal half-life following intravenous administration is 22 hours. The terminal half-life following inhalation in contrast is about 45 hours, indicating that the latter is determined by absorption rather than by elimination processes.
- Clearance
Total clearance of olodaterol in healthy volunteers is 872 mL/min, and renal clearance is 173 mL/min.
- Adverse Effects
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Adverse drug reactions that occurred at a frequency greater than 2% include nasopharyngitis (11.3%), upper respiratory tract infection (8.2%), bronchitis (4.7%), urinary tract infection (2.5%), cough (4.2%), dizziness (2.3%), rash (2.2%), diarrhea (2.9%), back pain (3.5%), and arthralgia (2.1%).
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 softwareAbatacept The metabolism of Olodaterol can be increased when combined with Abatacept. Abiraterone The metabolism of Olodaterol can be decreased when combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Olodaterol. Acebutolol The therapeutic efficacy of Olodaterol can be decreased when used in combination with Acebutolol. Aceclofenac The risk or severity of hypertension can be increased when Aceclofenac is combined with Olodaterol. - Food Interactions
- 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 Olodaterol hydrochloride 65R445W3V9 869477-96-3 KCEHVJZZIGJAAW-FERBBOLQSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Striverdi Respimat Spray, metered 2.5 ug/1 Respiratory (inhalation) Boehringer Ingelheim Pharmaceuticals, Inc. 2014-08-01 Not applicable US 
Striverdi Respimat Solution 2.5 mcg / act Respiratory (inhalation) Boehringer Ingelheim (Canada) Ltd Ltee Not applicable Not applicable Canada 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Inspiolto Respimat Olodaterol hydrochloride (2.5 mcg / act) + Tiotropium bromide monohydrate (2.5 mcg / act) Solution Respiratory (inhalation) Boehringer Ingelheim (Canada) Ltd Ltee 2015-05-29 Not applicable Canada SPIOLTO RESPIMAT Olodaterol hydrochloride (2.5 mcg) + Tiotropium bromide monohydrate (2.5 mcg) Solution Respiratory (inhalation) Boehringer Ingelheim International Gmbh 2020-09-18 Not applicable Italy 
SPIOLTO RESPIMAT Olodaterol hydrochloride (2.5 mcg) + Tiotropium bromide monohydrate (2.5 mcg) Solution Respiratory (inhalation) Boehringer Ingelheim International Gmbh 2020-09-18 Not applicable Italy SPIOLTO RESPIMAT Olodaterol hydrochloride (2.5 mcg) + Tiotropium bromide monohydrate (2.5 mcg) Solution Respiratory (inhalation) Boehringer Ingelheim International Gmbh 2020-09-18 Not applicable Italy SPIOLTO RESPIMAT Olodaterol hydrochloride (2.5 mcg) + Tiotropium bromide monohydrate (2.5 mcg) Solution Respiratory (inhalation) Boehringer Ingelheim International Gmbh 2020-09-18 Not applicable Italy
Categories
- ATC Codes
- R03AL06 — Olodaterol and tiotropium 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
- Adrenergic Agonists
- Adrenergic beta-1 Receptor Agonists
- Adrenergic beta-2 Receptor Agonists
- Adrenergic beta-Agonists
- Adrenergics, Inhalants
- Agents producing tachycardia
- Agents that produce hypertension
- Agents to Treat Airway Disease
- Anti-Asthmatic Agents
- Autonomic Agents
- Bronchodilator Agents
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 Substrates
- Drugs for Obstructive Airway Diseases
- Heterocyclic Compounds, Fused-Ring
- Long-acting beta-adrenoceptor agonists
- Oxazines
- Peripheral Nervous System Agents
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Respiratory System Agents
- Selective Beta 2-adrenergic Agonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzoxazinones. These are organic compounds containing a benzene fused to an oxazine ring (a six-member aliphatic ring with four carbon atoms, one oxygen atom, and one nitrogen atom) bearing a ketone group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzoxazines
- Sub Class
- Benzoxazinones
- Direct Parent
- Benzoxazinones
- Alternative Parents
- Amphetamines and derivatives / Benzomorpholines / Phenylpropanes / Phenoxy compounds / Methoxybenzenes / Anisoles / 1-hydroxy-2-unsubstituted benzenoids / Alkyl aryl ethers / Aralkylamines / Secondary carboxylic acid amides show 12 more
- Substituents
- 1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / Alcohol / Alkyl aryl ether / Amine / Amino acid or derivatives / Amphetamine or derivatives / Anisole / Aralkylamine / Aromatic alcohol show 28 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- aromatic ether, secondary alcohol, phenols, secondary amino compound, benzoxazine (CHEBI:82700)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- VD2YSN1AFD
- CAS number
- 868049-49-4
- InChI Key
- COUYJEVMBVSIHV-SFHVURJKSA-N
- InChI
- InChI=1S/C21H26N2O5/c1-21(2,10-13-4-6-15(27-3)7-5-13)22-11-18(25)16-8-14(24)9-17-20(16)28-12-19(26)23-17/h4-9,18,22,24-25H,10-12H2,1-3H3,(H,23,26)/t18-/m0/s1
- IUPAC Name
- 6-hydroxy-8-[(1R)-1-hydroxy-2-{[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino}ethyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one
- SMILES
- COC1=CC=C(CC(C)(C)NC[C@H](O)C2=C3OCC(=O)NC3=CC(O)=C2)C=C1
References
- General References
- Bouyssou T, Casarosa P, Naline E, Pestel S, Konetzki I, Devillier P, Schnapp A: Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models. J Pharmacol Exp Ther. 2010 Jul;334(1):53-62. doi: 10.1124/jpet.110.167007. Epub 2010 Apr 6. [Article]
- Bouyssou T, Hoenke C, Rudolf K, Lustenberger P, Pestel S, Sieger P, Lotz R, Heine C, Buttner FH, Schnapp A, Konetzki I: Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy. Bioorg Med Chem Lett. 2010 Feb 15;20(4):1410-4. doi: 10.1016/j.bmcl.2009.12.087. Epub 2010 Jan 4. [Article]
- Koch A, Pizzichini E, Hamilton A, Hart L, Korducki L, De Salvo MC, Paggiaro P: Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat(R) versus placebo and formoterol twice daily in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis. 2014 Jul 5;9:697-714. doi: 10.2147/COPD.S62502. eCollection 2014. [Article]
- Gibb A, Yang LP: Olodaterol: first global approval. Drugs. 2013 Nov;73(16):1841-6. doi: 10.1007/s40265-013-0137-9. [Article]
- Deeks ED: Olodaterol: a review of its use in chronic obstructive pulmonary disease. Drugs. 2015 Apr;75(6):665-73. doi: 10.1007/s40265-015-0371-4. [Article]
- External Links
- KEGG Drug
- D10145
- PubChem Compound
- 11504295
- PubChem Substance
- 310265008
- ChemSpider
- 9679097
- 1546059
- ChEBI
- 82700
- ChEMBL
- CHEMBL605846
- ZINC
- ZINC000034636383
- PDBe Ligand
- DZQ
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Olodaterol
- PDB Entries
- 8jjl
- FDA label
- Download (746 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Basic Science Chronic Obstructive Pulmonary Disease (COPD) 2 4 Completed Treatment Asthma 1 4 Completed Treatment Chronic Obstructive Pulmonary Disease (COPD) 8 4 Terminated Other Chronic Obstructive Pulmonary Disease (COPD) 1 4 Withdrawn Other Chronic Obstructive Pulmonary Disease (COPD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Oral Solution Respiratory (inhalation) 0.0025 mg/actuation Aerosol, metered Respiratory (inhalation) Solution Respiratory (inhalation) 0.0025 mg Solution Respiratory (inhalation) Spray, metered Respiratory (inhalation) Solution Respiratory (inhalation) 2.5 UG Aerosol Respiratory (inhalation) 2.5 MCG Solution Buccal 0.227 mg Solution Respiratory (inhalation) 2.5 mcg / act Solution Respiratory (inhalation) 2.5 MICROGRAMMI Spray, metered Respiratory (inhalation) 2.5 ug/1 Solution Respiratory (inhalation) 2.5 Mikrogramm Solution Respiratory (inhalation) 2.5 mcg Spray, metered Respiratory (inhalation) 2.5 mcg/1dose Aerosol Respiratory (inhalation) - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region USRE39820 Yes 2007-09-04 2018-07-30 US US6453795 Yes 2002-09-24 2017-06-05 US US8733341 Yes 2014-05-27 2031-04-16 US US9027967 Yes 2015-05-12 2027-10-01 US US7104470 Yes 2006-09-12 2017-04-04 US US7246615 Yes 2007-07-24 2016-12-01 US US7896264 Yes 2011-03-01 2025-11-26 US US7988001 Yes 2011-08-02 2022-02-04 US US7802568 Yes 2010-09-28 2019-08-26 US US6149054 Yes 2000-11-21 2017-06-16 US US6726124 Yes 2004-04-27 2017-04-04 US US7396341 Yes 2008-07-08 2027-04-10 US US6846413 Yes 2005-01-25 2019-02-28 US US6176442 Yes 2001-01-23 2016-12-01 US US7837235 Yes 2010-11-23 2028-09-13 US US5964416 Yes 1999-10-12 2017-04-04 US US7284474 Yes 2007-10-23 2025-02-26 US US6977042 Yes 2005-12-20 2019-02-28 US US6988496 Yes 2006-01-24 2020-08-23 US US8044046 No 2011-10-25 2023-11-10 US US8034809 No 2011-10-11 2025-05-12 US US7220742 No 2007-05-22 2025-05-12 US US7491719 No 2009-02-17 2023-11-10 US US7056916 No 2006-06-06 2023-12-07 US US7727984 No 2010-06-01 2023-11-10 US US7786111 No 2010-08-31 2023-11-10 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0703 mg/mL ALOGPS logP 2.02 ALOGPS logP 1.19 Chemaxon logS -3.7 ALOGPS pKa (Strongest Acidic) 9.22 Chemaxon pKa (Strongest Basic) 9.84 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 100.05 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 106.9 m3·mol-1 Chemaxon Polarizability 41.34 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-1293000000-1e2c29e62e006754a844 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-05n0-0049000000-36447900007f80363443 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03du-1918000000-1c9589df498ec997d1cb Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-072j-4962000000-52f167dd0807ddfc892b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-03fu-0915000000-4712cc53a044fd776b02 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-2915000000-a0aff5d26586e157d925 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 198.9135 predictedDeepCCS 1.0 (2019) [M+H]+ 201.27148 predictedDeepCCS 1.0 (2019) [M+Na]+ 207.61903 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- 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
References
- Bouyssou T, Casarosa P, Naline E, Pestel S, Konetzki I, Devillier P, Schnapp A: Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models. J Pharmacol Exp Ther. 2010 Jul;334(1):53-62. doi: 10.1124/jpet.110.167007. Epub 2010 Apr 6. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Olodaterol FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
Drug created at June 26, 2015 18:38 / Updated at February 20, 2024 23:54