Olodaterol

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Olodaterol
Olodaterol skeletal.svg
Systematic (IUPAC) name
6-hydroxy-8-{(1R)-1-hydroxy-2-{[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino}ethyl}-4H-1,4-benzoxazin-3-one
Clinical data
Trade names Striverdi Respimat
AHFS/Drugs.com UK Drug Information
Pregnancy
category
  • US: C (Risk not ruled out)
  • No experience
Legal status
  • UK: POM (Prescription only)
  • US: ℞-only
  • ℞ (Prescription only)
Routes of
administration		 Inhalation (MDI)
Pharmacokinetic data
Bioavailability ~30% (inhalation)[1]
Protein binding ~60%
Metabolism Hepatic
Biological half-life 7.5 hours
Excretion Feces (53%), urine (38%) — following IV administration
Identifiers
CAS Number 868049-49-4
ATC code R03AC19 (WHO)
PubChem CID: 11504295
IUPHAR/BPS 7543
ChemSpider 9679097
UNII VD2YSN1AFD
ChEBI CHEBI:82700 YesY
ChEMBL CHEMBL605846
Synonyms BI 1744 CL
Chemical data
Formula C21H26N2O5
Molecular mass 386.44 g/mol
  • CC(C)(CC1=CC=C(C=C1)OC)NCC(C2=CC(=CC3=C2OCC(=O)N3)O)O
  • 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
  • Key:COUYJEVMBVSIHV-SFHVURJKSA-N

Olodaterol (trade name Striverdi Respimat STRIH-ver-dee-RES-peh-mat) is an ultra-long-acting β adrenoreceptor agonist (ultra-LABA) used as an inhalation for treating patients with chronic obstructive pulmonary disease (COPD), manufactured by Boehringer Ingelheim.[2]

Medical uses

Olodaterol is a once-daily maintenance bronchodilator treatment of airflow obstruction in patients with COPD including chronic bronchitis and/or emphysema, and is administered in an inhaler called Respimat Soft Mist Inhaler.[3][4][5][6][7][8]

As of December 2013, olodaterol is not approved for the treatment of asthma. Olodaterol monotherapy was previously evaluated in four Phase II studies in asthma patients. However, currently there are no Phase III studies planned for olodaterol monotherapy in patients with asthma.[citation needed]

Adverse effects

Adverse effects generally were rare and mild in clinical studies. Most common, but still affecting no more than 1% of patients, were nasopharyngitis (running nose), dizziness and rash. To judge from the drug's mechanism of action and from experiences with related drugs, hypertension (high blood pressure), tachycardia (fast heartbeat), hypokalemia (low blood levels of potassium), shaking, etc., might occur in some patients, but these effects have rarely, if at all, been observed in studies.[2]

Interactions

Based on theoretical considerations, co-application of other beta-adrenoceptor agonists, potassium lowering drugs (e.g. corticosteroids, many diuretics, and theophylline), tricyclic antidepressants, and monoamine oxidase inhibitors could increase the likelihood of adverse effects to occur. Beta blockers, a group of drugs for the treatment of hypertension (high blood pressure) and various conditions of the heart, could reduce the efficacyz of olodaterol.[2] Clinical data on the relevance of such interactions are very limited.

Pharmacology

Mechanism of action

Like all β adrenoreceptor agonists, olodaterol mimics the effect of epinephrine at β2 receptors in the lung, which causes the bronchi to relax and reduces their resistance to airflow.[4]

Olodaterol is a nearly full β2 agonist, having 88% intrinsic activity compared to the gold standard isoprenaline/isoproterenol). Its half maximal effective concentration (EC50) is 0.1 nM. It has a higher in vitro selectivity for β2 receptors than the related drugs formoterol and salmeterol: 241-fold versus β1 and 2299-fold versus β3 adrenergic receptors.[3] The high β2/β1 selectivity may account for the apparent lack of tachycardia in clinical trials, which is mediated by β1 receptors on the heart.

Pharmacokinetics

Olodaterol is substantially metabolized by glucuronidation (UGT2B7, UGT1A1, UGT1A9) and O-demethylation (CYP2C8, CYP2C9).[1]

Pharmadynamics

Once bound to a β2 receptor, an olodaterol molecule stays there for hours — its dissociation half-life is 17.8 hours —, which allows for once-a-day application of the drug[4] like with indacaterol. Other related compounds generally have a shorter duration of action and have to be applied twice daily (e.g. formoterol, salmeterol). Still others (e. g. salbutamol/аlbuterol, fenoterol) have to be applied three or four times a day for continuous action, which can also be an advantage for patients who need to apply β2 agonists only occasionally, for example in an asthma attack.[9]

History

On 29 January 2013 the U.S. Food and Drug Administration (FDA) Pulmonary-Allergy Drugs Advisory Committee (PADAC) recommended that the clinical data included in the new drug application (NDA) for olodaterol provide substantial evidence of safety and efficacy to support the approval of olodaterol as a once-daily maintenance bronchodilator treatment for airflow obstruction in patients with COPD.[10]

On 18 October 2013 approval of olodaterol in the first three European countries — the United Kingdom, Denmark and Iceland — was announced by the manufacturer.[11]

On July 31, 2014 the U.S. Food and Drug Administration approved Striverdi Respimat (olodaterol inhalation spray) to treat patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema that are experiencing airflow obstruction.[12]

References

  1. ↑ 1.0 1.1 Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ 2.0 2.1 2.2 Striverdi UK Drug Information
  3. ↑ 3.0 3.1 Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ 4.0 4.1 4.2 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Joos G, Aumann JL, Coeck C, et al. ATS 2012 Abstract: Comparison of 24-Hour FEV1 Profile for Once-Daily versus Twice-Daily Treatment with Olodaterol, A Novel Long-Acting ß2-Agonist, in Patients with COPD[dead link]
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ van Noord JA, Korducki L, Hamilton AL and Koker P. Four Weeks Once Daily Treatment with BI 1744 CL, a Novel Long-Acting ß2-Agonist, is Effective in COPD Patients. Am. J. Respir. Crit. Care Med. 2009; 179: A6183
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

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