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{{drugbox
{{Drugbox
| IUPAC_name       = 4-(4-benzhydryloxy-1-piperidyl)-1-<br>(4-tert-butylphenyl)butan-1-one
| verifiedrevid = 439227374
| image             = Ebastine.svg
| IUPAC_name = 4-(4-benzhydryloxy-1-piperidyl)-1-(4-tert-butylphenyl)butan-1-one
| CAS_number        = 90729-43-4
| image = Ebastine.svg
| ATC_prefix        = R06
 
| ATC_suffix        = AX22
<!--Clinical data-->
| PubChem          = 3191
| tradename =
| DrugBank          =  
| Drugs.com = {{drugs.com|international|ebastine}}
| C = 32 | H = 39 | N = 1 | O = 2
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| molecular_weight = 469.658 g/mol
| pregnancy_US = <!-- A / B            / C / D / X -->
| bioavailability   =  
| pregnancy_category =
| protein_bound     = Greater than 95%
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| metabolism       = [[Liver|Hepatic]] ([[CYP3A4]]-mediated), to [[carebastine]]
| legal_CA = <!--            / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL        / P      / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC                  / Rx-only  / Schedule I, II, III, IV, V -->
| legal_status =  
| routes_of_administration = Oral
 
<!--Pharmacokinetic data-->
| bioavailability =
| protein_bound = Greater than 95%
| metabolism = [[Liver|Hepatic]] ([[CYP3A4]]-mediated), to [[carebastine]]
| elimination_half-life = 15 to 19 hours (carebastine)
| elimination_half-life = 15 to 19 hours (carebastine)
| excretion         =  
| excretion =
| pregnancy_AU      =  <!-- A / B1 / B2 / B3 / C / D / X -->
 
| pregnancy_US      = <!-- A / B            / C / D / X -->
<!--Identifiers-->
| pregnancy_category=
| CAS_number_Ref = {{cascite|correct|??}}
| legal_AU          = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| CAS_number = 90729-43-4
| legal_CA          = <!--             / Schedule I, II, III, IV, V, VI, VII, VIII -->
| ATC_prefix = R06
| legal_UK          = <!-- GSL        / P      / POM / CD / Class A, B, C -->
| ATC_suffix = AX22
| legal_US          = <!-- OTC                  / Rx-only  / Schedule I, II, III, IV, V -->
| PubChem = 3191
| legal_status      =  
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| routes_of_administration = Oral
| DrugBank =   
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3079
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = TQD7Q784P1
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 305660
 
<!--Chemical data-->
| C=32 | H=39 | N=1 | O=2
| molecular_weight = 469.658 g/mol
| smiles = O=C(c1ccc(cc1)C(C)(C)C)CCCN4CCC(OC(c2ccccc2)c3ccccc3)CC4
| InChI = 1/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
| InChIKey = MJJALKDDGIKVBE-UHFFFAOYAY
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MJJALKDDGIKVBE-UHFFFAOYSA-N
}}
 
'''Ebastine''' (trade names '''Evastin''', '''Kestine''', '''Ebastel''', '''Aleva''', '''Ebatrol''') is a H<sub>1</sub> [[antihistamine]] with low potential for causing drowsiness.
 
It does not penetrate the [[blood–brain barrier]] to a significant amount and thus combines an effective block of the [[histamine H1 receptor|H<sub>1</sub> receptor]] in peripheral [[biological tissue|tissue]] with a low incidence of central side effects, i.e. seldom causing sedation or drowsiness.<ref name="Tagawa 2001" /><ref name="Arzneistoff-Profile" /><ref name="Bousquet 1999" />
 
The patent in which the structure of ebastine is first mentioned is {{patent|EP|134124}} in Europe and {{patent|US|4550116}} in the US. The substance is often provided in [[micronise]]d form due to poor water solubility.
 
==Uses and availability==
Ebastine is a second-generation H1 receptor antagonist that is indicated mainly for allergic [[rhinitis]] and chronic idiopathic [[urticaria]].<ref name="Van Cauwenberge 2004" /> It is available in 10 and 20&nbsp;mg tablets<ref name="Sastre 2008" /> and as fast-dissolving tablets,<ref name="pmid 17697901" /> as well as in pediatric syrup. It has a recommended flexible daily dose of 10 or 20&nbsp;mg, depending on disease severity.
 
Ebastine is available in different formulations (tablets, fast dissolving tablets and syrup) and commercialized under different brand names around the world, '''Ebet''', '''Ebastel FLAS''', '''Kestine''', '''KestineLIO''', '''KestinLYO''', '''EstivanLYO''', '''Evastel Z''', '''Ebatrol''', etc.
 
==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.
[[File:Carebastine skeletal.svg|thumb|left|Carebastine, the active metabolite]]
{{clear left}}
 
==Efficacy==
Data from over 8,000 patients in more than 40 clinical trials{{failed verification|date=March 2014}} and studies<ref name="Bousquet 1999" /><ref name="Van Cauwenberge 2004" /><ref name="Sastre 2008" /><ref name="Ratner 2005" /><ref name="pmid 17563125" /><ref name="Gehanno 1996" /> 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<ref name="Sastre 2008" /> and no sedation<ref name="Sastre 2008" /> worse than [[placebo]],<ref name="Arzneistoff-Profile" /> and cardiac safety, that is, no [[QT prolongation]].<ref name="Sastre 2008" /> 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.<ref name="Arzneistoff-Profile" />
 
==References==
{{reflist|2|refs=
 
<ref name="Gehanno 1996">{{cite journal|last=Gehanno |first=P |last2=Bremard-Oury |first2=C |last3=Zeisser |first3=P |title=Comparison of ebastine to cetirizine in seasonal allergic rhinitis in adults |journal=Annals of Allergy, Asthma and Immunol |year=1996 |volume=76 |issue=6 |pages=507–12 |pmid=8673684 |doi=10.1016/S1081-1206(10)63269-3}}</ref>
 
<ref name="Bousquet 1999">{{cite journal|last=Bousquet |first=J |last2=Gaudaño |first2=EM |last3=Palama Carlos |first3=AG |title=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 |journal=Allergy |year=1999 |volume=54 |issue=6 |pages=562–568 |pmid=10435469 |doi=10.1034/j.1398-9995.1999.00984.x}}</ref>
 
<ref name="Tagawa 2001">{{cite journal|last=Tagawa |first=M |last2=Kano |first2=M |last3=Okamura |first3=N |title=Neuroimaging of histamine H1-receptor occupancy in human brain by positron emission tomography (PET): a comparative study of ebastine, a second-generation antihistamine, and (+)-clorphrniramine, a classical antihistamine |journal=[[Br J Clin Pharmacol]] |year=2001 |volume=52 |issue=5 |pages=501–509 |pmc=2014616 |pmid=11736858 |doi=10.1046/j.1365-2125.2001.01471.x}} {{open access}}</ref>
 
<ref name="Van Cauwenberge 2004">{{cite journal|last=Van Cauwenberge |first=P |last2=de Belder |first2=T |last3=Sys |first3=L |title=A review of the second-generation antihistamine ebastine for the treatment of allergic disorders |journal=Exp Rew Pharmacother |year=2004 |volume=5 |issue=8 |pages=1807–13 |pmid=15264995 |doi=10.1517/14656566.5.8.1807}}</ref>
 
<ref name="Ratner 2005">{{cite journal|last=Ratner |first=P |last2=Falqués |first2=M |last3=Chuecos |first3=F |title=Meta-analysis of the efficacy of ebastine 20 mg compared to loratadine 10 mg and placebo in the symptomatic treatment of seasonal allergic rhinitis |journal=Int Arch Allergy Immunol |year=2005 |volume=138 |issue=4 |pages=312–8 |pmid=16224195 |doi=10.1159/000088869}}</ref>
 
<ref name="pmid 17563125">{{cite journal|last=Antonijoan |first=RM |last2=García-Gea |first2=C |last3=Puntes |first3=M |title=A comparison of ebastine 10 mg fast-dissolving tablet with oral desloratadine and placebo in inhibiting the cutaneous reaction to histamine in healthy adults |journal=Clin Drug Invest |year=2007 |volume=27 |issue=7 |pages=453–61 |pmid=17563125 |doi=10.2165/00044011-200727070-00002}}</ref>
 
<ref name="pmid 17697901">{{cite journal|last=Antonijoan |first=R |last2=García-Gea |first2=C |last3=Puntes |first3=M |title=Comparison of inhibition of cutaneous histamine reaction of ebastine fast-dissolving tablet (20 mg) versus desloratadine capsules (5 mg): a randomized, double-blind, double-dummy, placebo-controlled, three period crossover study in healthy, nonatopic adults |journal=Clin Ther |year=2007 |volume=29 |issue=5 |pages=814–22 |pmid=17697901 |doi=10.1016/j.clinthera.2007.05.001}}</ref>
 
<ref name="Sastre 2008">{{cite journal|last=Sastre |first=J |title=Ebastine in allergic rhinitis and chronic idiopathic urticaria |journal=Allergy |year=2008 |volume=63 |issue=Suppl 89 |pages=1–20 |doi=10.1111/j.1398-9995.2008.01897.x |pmid=19032340}}</ref>
 
<ref name="Arzneistoff-Profile">{{cite book|title=Arzneistoff-Profile|editor=Dinnendahl, V, Fricke, U|publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|year=2010|edition=23|volume=4|isbn=978-3-7741-98-46-3|language=German}}</ref>
 
}}
}}
'''Ebastine''' (trade names '''Kestine''', '''Evastin''', '''Ebastel''', '''Aleva''') is a [[sedative|non-sedating]] H<sub>1</sub> [[antihistamine]].


It does not penetrate the [[blood-brain barrier]] and thus allows an effective block of the [[histamine H1 receptor|H<sub>1</sub> receptor]] in peripheral [[biological tissue|tissue]] without a central side effect, i.e not causing sedation or drowsiness.
* {{cite journal|last=Salvà |first=M |last2=Carreño |first2=B |last3=Pintos |first3=M |title=Phase I, single dose, open label, randomized, crossover bioequivalence studies of ebastine 10 mg and 20 mg regular tablets vs 10 and 20 mg fast-dissolving tablets in healthy male volunteers |journal=J Invest Allergol Clin Immunol |year=2004 |volume=14 |issue=4 (Suppl 1) |page=S5}}
 
* {{cite journal|last=Peyri |first=J |last2=Vidal |first2=J |last3=Marrón |first3=J |last4=Fonseca |first4=E. |last5=Suárez |first5=E. |last6=Ledo |first6=A. |last7=Zayas |first7=J. M. |last8=Luria |first8=X. |title=Ebastine in chronic urticaria: a double-blind placebo controlled study |journal=J Dermatol Treat |year=1991 |volume=2 |issue=2 |pages=51–3 |doi=10.3109/09546639109086774}}


==External links==
==External links==
*{{cite web | url = http://home.intekom.com/pharm/lennon/kestine.html | title = KESTINE&reg; Package Insert | date = October 24, 1997 | accessdate = 2007-04-01 | publisher = [[South Africa]]n Electronic Package Inserts}}
*{{cite web | url = http://home.intekom.com/pharm/lennon/kestine.html | title = KESTINE Package Insert | date = 1997-10-24 | accessdate = 2007-04-01 | publisher = [[South Africa]]n Electronic Package Inserts}}


{{Antihistamines}}
{{Antihistamines}}
{{Histaminergics}}


[[Category:Antihistamines]]
[[Category:H1 receptor antagonists]]
 
[[Category:Ethers]]
{{pharma-stub}}
[[Category:Piperidines]]
 
[[Category:Aromatic ketones]]
[[es:Ebastina]]
[[th:อีบาสทีน]]
{{WikiDoc Sources}}

Revision as of 17:24, 7 April 2015

Ebastine
File:Ebastine.svg
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
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC32H39NO2
Molar mass469.658 g/mol
3D model (JSmol)
  (verify)

Ebastine (trade names Evastin, Kestine, Ebastel, Aleva, Ebatrol) is a H1 antihistamine with low potential for causing drowsiness.

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]

The patent in which the structure of ebastine is first mentioned is Template:Patent in Europe and Template:Patent in the US. The substance is often provided in micronised form due to poor water solubility.

Uses and availability

Ebastine is a second-generation H1 receptor antagonist that is indicated mainly for allergic rhinitis and chronic idiopathic urticaria.[4] It is available in 10 and 20 mg tablets[5] and as fast-dissolving tablets,[6] as well as in pediatric syrup. It has a recommended flexible daily dose of 10 or 20 mg, depending on disease severity.

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

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.

File:Carebastine skeletal.svg
Carebastine, the active metabolite

Efficacy

Data from over 8,000 patients in more than 40 clinical trials[not in citation given] and studies[3][4][5][7][8][9] 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[5] and no sedation[5] worse than placebo,[2] and cardiac safety, that is, no QT prolongation.[5] 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.[2]

References

  1. ↑ Tagawa, M; Kano, M; Okamura, N (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 (+)-clorphrniramine, a classical antihistamine". Br J Clin Pharmacol. 52 (5): 501–509. doi:10.1046/j.1365-2125.2001.01471.x. PMC 2014616. PMID 11736858. open access publication – free to read
  2. ↑ 2.0 2.1 2.2 Dinnendahl, V, Fricke, U, ed. (2010). Arzneistoff-Profile (in German). 4 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-98-46-3.
  3. ↑ 3.0 3.1 Bousquet, J; Gaudaño, EM; Palama Carlos, AG (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". Allergy. 54 (6): 562–568. doi:10.1034/j.1398-9995.1999.00984.x. PMID 10435469.
  4. ↑ 4.0 4.1 Van Cauwenberge, P; de Belder, T; Sys, L (2004). "A review of the second-generation antihistamine ebastine for the treatment of allergic disorders". Exp Rew Pharmacother. 5 (8): 1807–13. doi:10.1517/14656566.5.8.1807. PMID 15264995.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 Sastre, J (2008). "Ebastine in allergic rhinitis and chronic idiopathic urticaria". Allergy. 63 (Suppl 89): 1–20. doi:10.1111/j.1398-9995.2008.01897.x. PMID 19032340.
  6. ↑ Antonijoan, R; García-Gea, C; Puntes, M (2007). "Comparison of inhibition of cutaneous histamine reaction of ebastine fast-dissolving tablet (20 mg) versus desloratadine capsules (5 mg): a randomized, double-blind, double-dummy, placebo-controlled, three period crossover study in healthy, nonatopic adults". Clin Ther. 29 (5): 814–22. doi:10.1016/j.clinthera.2007.05.001. PMID 17697901.
  7. ↑ Ratner, P; Falqués, M; Chuecos, F (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". Int Arch Allergy Immunol. 138 (4): 312–8. doi:10.1159/000088869. PMID 16224195.
  8. ↑ Antonijoan, RM; García-Gea, C; Puntes, M (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". Clin Drug Invest. 27 (7): 453–61. doi:10.2165/00044011-200727070-00002. PMID 17563125.
  9. ↑ Gehanno, P; Bremard-Oury, C; Zeisser, P (1996). "Comparison of ebastine to cetirizine in seasonal allergic rhinitis in adults". Annals of Allergy, Asthma and Immunol. 76 (6): 507–12. doi:10.1016/S1081-1206(10)63269-3. PMID 8673684.
  • Salvà, M; Carreño, B; Pintos, M (2004). "Phase I, single dose, open label, randomized, crossover bioequivalence studies of ebastine 10 mg and 20 mg regular tablets vs 10 and 20 mg fast-dissolving tablets in healthy male volunteers". J Invest Allergol Clin Immunol. 14 (4 (Suppl 1)): S5.
  • Peyri, J; Vidal, J; Marrón, J; Fonseca, E.; Suárez, E.; Ledo, A.; Zayas, J. M.; Luria, X. (1991). "Ebastine in chronic urticaria: a double-blind placebo controlled study". J Dermatol Treat. 2 (2): 51–3. doi:10.3109/09546639109086774.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Ebastine&oldid=1084193"