Ebastine

Ebastine is a H1 antihistamine with low potential for causing drowsiness.

Ebastine
Clinical data
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Pharmacokinetic data
Protein bindingGreater than 95%
MetabolismHepatic (CYP3A4-mediated), to carebastine
Elimination half-life15 to 19 hours (carebastine)
Identifiers
IUPAC name
  • 4-(4-benzhydryloxy-1-piperidyl)-1-(4-tert-butylphenyl)butan-1-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.106.831
Chemical and physical data
FormulaC32H39NO2
Molar mass469.669 g·mol−1
3D model (JSmol)
SMILES
  • O=C(c1ccc(cc1)C(C)(C)C)CCCN4CCC(OC(c2ccccc2)c3ccccc3)CC4
InChI
  • InChI=1S/C32H39NO2/c1-32(2,3)28-18-16-25(17-19-28)30(34)15-10-22-33-23-20-29(21-24-33)35-31(26-11-6-4-7-12-26)27-13-8-5-9-14-27/h4-9,11-14,16-19,29,31H,10,15,20-24H2,1-3H3 Y
  • Key:MJJALKDDGIKVBE-UHFFFAOYSA-N Y
  (verify)

It does not penetrate the blood–brain barrier to a significant amount and thus combines an effective block of the H1 receptor in peripheral tissue with a low incidence of central side effects, i.e. seldom causing sedation or drowsiness.[1][2][3]

It was patented in 1983 by Almirall S.A and came into medical use in 1990.[4] The substance is often provided in micronised form due to poor water solubility.

Uses

Ebastine is a second-generation H1 receptor antagonist that is indicated mainly for allergic rhinitis and chronic idiopathic urticaria.[5] It is available in 10 and 20 mg tablets[6] and as fast-dissolving tablets,[7] as well as in pediatric syrup. It has a recommended flexible daily dose of 10 or 20 mg, depending on disease severity.

Data from over 8,000 patients in more than 40 clinical trials and studies[3][5][6][8][9][10] suggest efficacy of ebastine in the treatment of intermittent allergic rhinitis, persistent allergic rhinitis and other indications.

Safety

Ebastine has shown overall safety and tolerability profile with no cognitive/psychomotor impairment[6] and no sedation[6] worse than placebo,[2] and cardiac safety, that is, no QT prolongation.[6] The incidence of most commonly reported adverse events was comparable between the ebastine and placebo groups, which confirms that ebastine has a favourable safety profile.

While experiments in pregnant animals showed no risk for the unborn, no such data are available in humans. It is not known whether ebastine passes into the breast milk.

Pharmacokinetic profile

After oral administration, ebastine undergoes extensive first-pass metabolism by hepatic cytochrome P450 3A4 into its active carboxylic acid metabolite, carebastine. This conversion is practically complete.

Carebastine, the active metabolite

Brand names

Ebastine is available in different formulations (tablets, fast dissolving tablets and syrup) and commercialized under different brand names around the world, Ebast, Ebatin, Ebatin Fast, Ebatrol, Atmos, Ebet, Ebastel FLAS, Kestine, KestineLIO, KestinLYO, EstivanLYO, Evastel Z,Tebast (SQUARE), Ebasten (ACI), etc.

References
  1. Tagawa M, Kano M, Okamura N, Higuchi M, Matsuda M, Mizuki Y, et al. (November 2001). "Neuroimaging of histamine H1-receptor occupancy in human brain by positron emission tomography (PET): a comparative study of ebastine, a second-generation antihistamine, and (+)-chlorpheniramine, a classical antihistamine". British Journal of Clinical Pharmacology. 52 (5): 501–9. doi:10.1046/j.1365-2125.2001.01471.x. PMC 2014616. PMID 11736858.
  2. Dinnendahl, V; Fricke, U, eds. (2010). Arzneistoff-Profile (in German). Vol. 4 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-98-46-3.
  3. Bousquet J, Gaudaño EM, Palma Carlos AG, Staudinger H (June 1999). "A 12-week, placebo-controlled study of the efficacy and safety of ebastine, 10 and 20 mg once daily, in the treatment of perennial allergic rhinitis. Multicentre Study Group". Allergy. 54 (6): 562–8. doi:10.1034/j.1398-9995.1999.00984.x. PMID 10435469. S2CID 24186838.
  4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 549. ISBN 9783527607495.
  5. Van Cauwenberge P, De Belder T, Sys L (August 2004). "A review of the second-generation antihistamine ebastine for the treatment of allergic disorders". Expert Opinion on Pharmacotherapy. 5 (8): 1807–13. doi:10.1517/14656566.5.8.1807. PMID 15264995. S2CID 24967427.
  6. Sastre J (December 2008). "Ebastine in allergic rhinitis and chronic idiopathic urticaria". Allergy. 63 Suppl 89 (Suppl 89): 1–20. doi:10.1111/j.1398-9995.2008.01897.x. PMID 19032340. S2CID 12474747.
  7. Antonijoan R, García-Gea C, Puntes M, Pérez J, Esbrí R, Serra C, et al. (May 2007). "Comparison of inhibition of cutaneous histamine reaction of ebastine fast-dissolving tablet (20 mg) versus desloratadine capsule (5 mg): a randomized, double-blind, double-dummy, placebo-controlled, three-period crossover study in healthy, nonatopic adults". Clinical Therapeutics. 29 (5): 814–822. doi:10.1016/j.clinthera.2007.05.001. PMID 17697901.
  8. Ratner P, Falqués M, Chuecos F, Esbrí R, Gispert J, Peris F, et al. (December 2005). "Meta-analysis of the efficacy of ebastine 20 mg compared to loratadine 10 mg and placebo in the symptomatic treatment of seasonal allergic rhinitis". International Archives of Allergy and Immunology. 138 (4): 312–8. doi:10.1159/000088869. PMID 16224195. S2CID 4126940.
  9. Antonijoan RM, García-Gea C, Puntes M, Valle M, Esbri R, Fortea J, Barbanoj MJ (2007). "A comparison of ebastine 10 mg fast-dissolving tablet with oral desloratadine and placebo in inhibiting the cutaneous reaction to histamine in healthy adults". Clinical Drug Investigation. 27 (7): 453–61. doi:10.2165/00044011-200727070-00002. PMID 17563125. S2CID 23324628.
  10. Gehanno P, Bremard-Oury C, Zeisser P (June 1996). "Comparison of ebastine to cetirizine in seasonal allergic rhinitis in adults". Annals of Allergy, Asthma & Immunology. 76 (6): 507–12. doi:10.1016/S1081-1206(10)63269-3. PMID 8673684.
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