Bepotastine

Identification

Name
Bepotastine
Accession Number
DB04890
Description

Bepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor. Bepotastine was approved in Japan for use in the treatment of allergic rhinitis and uriticaria/puritus in July 2000 and January 2002, respectively, and is marketed by Tanabe Seiyaku Co., Ltd. under the brand name Talion. It is available in oral and opthalmic dosage forms in Japan. The opthalmic solution is FDA approved since Sept 8, 2009 and is under the brand name Bepreve.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 388.888
Monoisotopic: 388.155370383
Chemical Formula
C21H25ClN2O3
Synonyms
  • bepotastina
  • Bepotastine
External IDs
  • TAU-284DS

Pharmacology

Indication

For the symptomatic treatment of itchy eyes (caused by IgE-induced mast cell degranulation) due to allergic conjunctivitis.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Bepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor. It belongs to the second-generation piperidine chemical class. It is a mast cell stabilizer and suppresses the migration of eosinophils into inflamed tissues. Furthermore, bepotastine does not interact with serotonin, muscarinic, benzodiazepine, and beta-adrenergic receptor that would otherwise result in adverse reactions such as dry mouth or sonmolence.
Onset of action = 0.25 hours; Duration of action = 12-24 hours;

Mechanism of action

Because of a type 1 hypersensitivity reaction cascade that is triggered by antigen exposure, allergic conjunctivitis occurs. Allergen exposure is followed by conjunctival mast cell degranulation and histamine released as a result of the formation of complementary IgE cross-links on the conjunctiva. Due to the release of histamine, symptoms such as itching can be observed. Bepotastine works to relieve itchy eyes by three primary mechanisms of action. It is a non-sedating, selective antagonist of the histamine 1 (H1) receptor, a mast cell stabilizer, and it suppresses the migration of eosinophils into inflamed tissues to prevent tissue damage and worsening of allergic inflammation of the conjunctiva.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Humans
Absorption

Tmax, after single dose, opthalmic = 1.2 hours; Cmax, 1.5%, opthalmic dose = 7.3 ±1.9 ng/mL; After 24 hours post-installation, levels of bepotastine are below quantifiable limit of 2 ng/mL. Minimal systemic absorption with opthalmic dosage form.

Volume of distribution
Not Available
Protein binding

55.4% mean plasma protein binding with 10 mg oral dose. Extent of protein binding is independent of plasma drug concentration.

Metabolism

Minimal metabolism via CYP enzymes

Route of elimination

When a oral dose of 2.5 - 40 mg bepotastine is given, 75%-90% of the dose was excreted unchanged in the urine by 24 hours.

Half-life

Elimination half life = 2.5 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Bepotastine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Bepotastine which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Bepotastine which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Bepotastine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Bepotastine which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Bepotastine which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Bepotastine which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Bepotastine which could result in a higher serum level.
AclidiniumBepotastine may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineBepotastine may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Bepotastine which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food. Orally formulated bepotastine bioavailability is not significantly impacted by food.

Products

Product Ingredients
IngredientUNIICASInChI Key
Bepotastine besilate6W18MO1QR3190786-44-8UDGHXQPQKQPSBB-BOXHHOBZSA-N
International/Other Brands
Talion
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BepreveSolution / drops15 mg/1mLOphthalmicIsta Pharmaceuticals, Inc2009-09-082014-09-30US flag
BepreveSolution1.5 %OphthalmicBausch & Lomb Inc2017-03-23Not applicableCanada flag
BepreveSolution / drops15 mg/1mLOphthalmicPhysicians Total Care, Inc.2011-09-26Not applicableUS flag
BepreveSolution / drops15 mg/1mLOphthalmicBausch & Lomb Incorporated2009-09-08Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzylethers
Direct Parent
Benzylethers
Alternative Parents
Amino fatty acids / Chlorobenzenes / Pyridines and derivatives / Piperidines / Aryl chlorides / Heteroaromatic compounds / Trialkylamines / Amino acids / Monocarboxylic acids and derivatives / Azacyclic compounds
show 7 more
Substituents
Amine / Amino acid / Amino acid or derivatives / Amino fatty acid / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzylether / Carbonyl group
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
HYD2U48IAS
CAS number
125602-71-3
InChI Key
YWGDOWXRIALTES-UHFFFAOYSA-N
InChI
InChI=1S/C21H25ClN2O3/c22-17-8-6-16(7-9-17)21(19-4-1-2-12-23-19)27-18-10-14-24(15-11-18)13-3-5-20(25)26/h1-2,4,6-9,12,18,21H,3,5,10-11,13-15H2,(H,25,26)
IUPAC Name
4-{4-[(4-chlorophenyl)(pyridin-2-yl)methoxy]piperidin-1-yl}butanoic acid
SMILES
OC(=O)CCCN1CCC(CC1)OC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1

References

Synthesis Reference

Tae Hee Ha, Chang Hee Park, Won Jeoung Kim, Soohwa Cho, Han Kyong Kim, Kwee Hyun Suh, "PROCESS FOR PREPARING BEPOTASTINE AND INTERMEDIATES USED THEREIN." U.S. Patent US20100168433, issued July 01, 2010.

US20100168433
General References
  1. Ohashi R, Kamikozawa Y, Sugiura M, Fukuda H, Yabuuchi H, Tamai I: Effect of P-glycoprotein on intestinal absorption and brain penetration of antiallergic agent bepotastine besilate. Drug Metab Dispos. 2006 May;34(5):793-9. Epub 2006 Feb 2. [PubMed:16455807]
  2. Andoh T, Kuraishi Y: Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice. Eur J Pharmacol. 2006 Oct 10;547(1-3):59-64. Epub 2006 Jul 25. [PubMed:16914135]
  3. Simons FE, Simons KJ: Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011 Dec;128(6):1139-1150.e4. doi: 10.1016/j.jaci.2011.09.005. Epub 2011 Oct 27. [PubMed:22035879]
  4. Wingard JB, Mah FS: Critical appraisal of bepotastine in the treatment of ocular itching associated with allergic conjunctivitis. Clin Ophthalmol. 2011;5:201-7. doi: 10.2147/OPTH.S8665. Epub 2011 Feb 15. [PubMed:21386912]
  5. FDA Approved Drug Products: Bepreve (bepotastine besilat) ophthalmic solution [Link]
Human Metabolome Database
HMDB0015600
KEGG Drug
D01654
PubChem Compound
2350
PubChem Substance
46504940
ChemSpider
2260
RxNav
863035
ChEBI
71204
ChEMBL
CHEMBL1201758
Therapeutic Targets Database
DCL000719
PharmGKB
PA164781356
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Bepotastine
AHFS Codes
  • 52:02.00 — Antiallergic Agents
FDA label
Download (161 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableHistamine Responsive Allergy Patients1
4CompletedTreatmentConjunctivitis, Seasonal Allergic2
4Unknown StatusTreatmentConjunctivitis, Seasonal Allergic1
3CompletedTreatmentAtopy / Skin Inflammation1
3CompletedTreatmentConjunctivitis, Seasonal Allergic2
3CompletedTreatmentPerennial Allergic Rhinitis (PAR)3
3CompletedTreatmentPruritus1
2CompletedTreatmentConjunctivitis, Seasonal Allergic1
2CompletedTreatmentSeasonal Allergic Rhinitis (SAR)3
2, 3CompletedTreatmentConjunctivitis allergic / Conjunctivitis, Seasonal Allergic1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • ISTA Pharmaceuticals
Dosage Forms
FormRouteStrength
SolutionOphthalmic1.5 %
Solution / dropsOphthalmic15 mg/1mL
SolutionConjunctival; Ophthalmic15 mg
Tablet, film coatedOral
SolutionOphthalmic15 mg
Prices
Unit descriptionCostUnit
Bepreve 1.5% eye drops10.8USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8784789No2014-07-222024-09-05US flag
US6780877No2004-08-242019-09-19US flag
US8877168No2014-11-042023-07-30US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0503 mg/mLALOGPS
logP3.64ALOGPS
logP0.55ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)4.1ChemAxon
pKa (Strongest Basic)9.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area62.66 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity105.1 m3·mol-1ChemAxon
Polarizability42.18 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9205
Blood Brain Barrier-0.5488
Caco-2 permeable-0.5304
P-glycoprotein substrateSubstrate0.6552
P-glycoprotein inhibitor IInhibitor0.8159
P-glycoprotein inhibitor IIInhibitor0.7308
Renal organic cation transporterInhibitor0.5948
CYP450 2C9 substrateNon-substrate0.7907
CYP450 2D6 substrateNon-substrate0.7496
CYP450 3A4 substrateNon-substrate0.5729
CYP450 1A2 substrateNon-inhibitor0.8235
CYP450 2C9 inhibitorNon-inhibitor0.8817
CYP450 2D6 inhibitorNon-inhibitor0.8289
CYP450 2C19 inhibitorNon-inhibitor0.8369
CYP450 3A4 inhibitorNon-inhibitor0.8711
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6461
Ames testNon AMES toxic0.8246
CarcinogenicityNon-carcinogens0.9647
BiodegradationNot ready biodegradable0.9929
Rat acute toxicity2.7211 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6558
hERG inhibition (predictor II)Inhibitor0.6222
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Andoh T, Kuraishi Y: Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice. Eur J Pharmacol. 2006 Oct 10;547(1-3):59-64. Epub 2006 Jul 25. [PubMed:16914135]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on October 21, 2007 10:29 / Updated on October 26, 2020 22:41

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