Olodaterol

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Olodaterol
Olodaterol skeletal.svg
Clinical data
Trade names Striverdi Respimat
Synonyms BI 1744 CL
AHFS/Drugs.com UK Drug Information
Pregnancy
category
  • US: C (Risk not ruled out)
  • No experience
Routes of
administration
Inhalation (MDI)
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability ~30% (inhalation)[1]
Protein binding ~60%
Metabolism Hepatic
Elimination half-life 7.5 hours
Excretion Feces (53%), urine (38%) — following IV administration
Identifiers
CAS Number
  • 868049-49-4
PubChem CID
  • 11504295
IUPHAR/BPS
  • 7543
ChemSpider
  • 9679097
UNII
  • VD2YSN1AFD
KEGG
  • D10145
ChEBI
  • CHEBI:82700 ☑Y
ChEMBL
  • CHEMBL605846
Chemical and physical data
Formula C21H26N2O5
Molar mass 386.44 g/mol
3D model (JSmol)
  • Interactive image

Olodaterol (trade name Striverdi Respimat /ˈstrɪvərdi ˈrɛspɪmæt/ STRIV-ər-dee RES-pim-at) 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 efficacy 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 β21 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. ^ a b "Striverdi Respimat (olodaterol) Inhalation Spray For Oral Inhalation. U.S. Full Prescribing Information" (PDF). Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877 USA. Retrieved 23 February 2016.
  2. ^ a b c Striverdi UK Drug Information
  3. ^ a b Bouyssou, T.; Casarosa, P.; Naline, E.; Pestel, S.; Konetzki, I.; Devillier, P.; Schnapp, A. (2010). "Pharmacological Characterization of Olodaterol, a Novel Inhaled 2-Adrenoceptor Agonist Exerting a 24-Hour-Long Duration of Action in Preclinical Models". Journal of Pharmacology and Experimental Therapeutics. 334 (1): 53–62. doi:10.1124/jpet.110.167007. PMID 20371707.
  4. ^ a b c Casarosa, P.; Kollak, I.; Kiechle, T.; Ostermann, A.; Schnapp, A.; Kiesling, R.; Pieper, M.; Sieger, P.; Gantner, F. (2011). "Functional and Biochemical Rationales for the 24-Hour-Long Duration of Action of Olodaterol" (PDF). Journal of Pharmacology and Experimental Therapeutics. 337 (3): 600–609. doi:10.1124/jpet.111.179259. PMID 21357659.
  5. ^ Bouyssou, T.; Hoenke, C.; Rudolf, K.; Lustenberger, P.; Pestel, S.; Sieger, P.; Lotz, R.; Heine, C.; Büttner, F. H.; Schnapp, A.; Konetzki, I. (2010). "Discovery of olodaterol, a novel inhaled β2-adrenoceptor agonist with a 24h bronchodilatory efficacy". Bioorganic & Medicinal Chemistry Letters. 20 (4): 1410–1414. doi:10.1016/j.bmcl.2009.12.087. PMID 20096576.
  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
  7. ^ Van Noord, J. A.; Smeets, J. J.; Drenth, B. M.; Rascher, J.; Pivovarova, A.; Hamilton, A. L.; Cornelissen, P. J. G. (2011). "24-hour Bronchodilation following a single dose of the novel β2-agonist olodaterol in COPD". Pulmonary Pharmacology & Therapeutics. 24 (6): 666–672. doi:10.1016/j.pupt.2011.07.006. PMID 21839850.
  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. ^ Haberfeld, H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 3-85200-196-X.
  10. ^ Hollis A (31 January 2013). "Panel Overwhelmingly Supports Boehringer COPD Drug Striverdi". FDA News/Drug Industry Daily.
  11. ^ "New once-daily Striverdi (olodaterol) Respimat gains approval in first EU countries". Boehringer-Ingelheim. 18 October 2013.
  12. ^ "FDA approves Striverdi Respimat to treat chronic obstructive pulmonary disease". FDA News/Drug Industry Daily. 31 July 2014.

External links

  • Official Site
  • Striverdi package leaflet (UK)
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