Identification

Name
Bilastine
Accession Number
DB11591
Type
Small Molecule
Groups
Approved, Investigational
Description

Bilastine is a novel new-generation antihistamine that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action.

Structure
Thumb
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BlextenTablet20 mgOralAralez Pharmaceuticals Trading Dac2016-12-02Not applicableCanada
International/Other Brands
Bilaxten (Faes Farma)
Categories
UNII
PA1123N395
CAS number
202189-78-4
Weight
Average: 463.622
Monoisotopic: 463.283492063
Chemical Formula
C28H37N3O3
InChI Key
ACCMWZWAEFYUGZ-UHFFFAOYSA-N
InChI
InChI=1S/C28H37N3O3/c1-4-34-20-19-31-25-8-6-5-7-24(25)29-26(31)22-14-17-30(18-15-22)16-13-21-9-11-23(12-10-21)28(2,3)27(32)33/h5-12,22H,4,13-20H2,1-3H3,(H,32,33)
IUPAC Name
2-[4-(2-{4-[1-(2-ethoxyethyl)-1H-1,3-benzodiazol-2-yl]piperidin-1-yl}ethyl)phenyl]-2-methylpropanoic acid
SMILES
CCOCCN1C(=NC2=CC=CC=C12)C1CCN(CCC2=CC=C(C=C2)C(C)(C)C(O)=O)CC1

Pharmacology

Indication

For symptomatic relief of nasal and non-nasal symptoms of seasonal rhinitis in patients 12 years of age and older and for symptomatic relief in chronic spontaneous urticaria in patients 18 years of age and older [Label].

Pharmacodynamics

Bilastine is an antiallergenic and acts to reduce allergic symptoms such as nasal congestion and urticaria [Label].

Mechanism of action

Bilastine is a selective histamine H1 receptor antagonist (Ki = 64nM) [Label]. During allergic response mast cells undergo degranulation which releases histamine and other subastances. By binding to and preventing activation of the H1 receptor, bilastine reduces the development of allergic symptoms due to the release of histamine from mast cells.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Bilastine has a Tmax of 1.13 h [Label]. The absolute bioavailability is 61%. No accumulation observed with daily dosing of 20-100 mg after 14 days. Cmax decreased by 25 % and 33% when taken with a low fat and high fat meal compared to fasted state. Administration with grapefruit juice decreased Cmax by 30%.

Volume of distribution
Not Available
Protein binding

Bilastine is 84-90% bound to human plasma proteins [Label].

Metabolism

Bilastine does not interact with the cytochrome P450 system and does not undergo significant metabolism in humans [Label].

Route of elimination

Bilastine is mainly excreted in the feces (66.5%) with some excreted in the urine (28.3%) [Label]. Nearly all is excreted as the parent compound.

Half life

The mean half life of elimination is 14.5h [Label].

Clearance

Bilastine has a total clearance is 9.20 L/h and a renal clearance of 8.7 L/h [Label].

Toxicity

The most common adverse effects experienced during clinical trials were abdominal pain, dizziness, headache, and somnolence [Label]. Bilastine is associated with Q/T prolongation. The no observed adverse effect level of bilastine is 1200 mg/kg/day in rats and 125 mg/kg/day in dogs [2].

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Bilastine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Bilastine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Bilastine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Bilastine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Bilastine.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Bilastine.
AlimemazineThe risk or severity of QTc prolongation can be increased when Alimemazine is combined with Bilastine.
AmiodaroneThe risk or severity of QTc prolongation can be increased when Bilastine is combined with Amiodarone.
AmitriptylineThe risk or severity of QTc prolongation can be increased when Bilastine is combined with Amitriptyline.
AmphetamineAmphetamine may decrease the sedative and stimulatory activities of Bilastine.
AnagrelideThe risk or severity of QTc prolongation can be increased when Bilastine is combined with Anagrelide.
Food Interactions
Not Available

References

General References
  1. Wang XY, Lim-Jurado M, Prepageran N, Tantilipikorn P, Wang de Y: Treatment of allergic rhinitis and urticaria: a review of the newest antihistamine drug bilastine. Ther Clin Risk Manag. 2016 Apr 13;12:585-97. doi: 10.2147/TCRM.S105189. eCollection 2016. [PubMed:27110120]
  2. Lucero ML, Arteche JK, Sommer EW, Casadesus A: Preclinical toxicity profile of oral bilastine. Drug Chem Toxicol. 2012 Jun;35 Suppl 1:25-33. doi: 10.3109/01480545.2012.682652. [PubMed:22616813]
External Links
Human Metabolome Database
HMDB0240232
PubChem Compound
185460
PubChem Substance
347827998
ChemSpider
161234
ChEBI
135954
ChEMBL
CHEMBL1742423
Wikipedia
Bilastine
ATC Codes
R06AX29 — Bilastine
AHFS Codes
  • 04:08.00 — Second Generation Antihistamines
FDA label
Download (550 KB)
MSDS
Download (200 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers1
1RecruitingBasic SciencePharmacokinetics1
1, 2CompletedTreatmentAllergic Rhinoconjunctivitis / Chronic Urticaria1
2CompletedTreatmentConjunctivitis, Seasonal Allergic1
2CompletedTreatmentConjunctivitis, Seasonal Allergic / Hypersensitivity / Pollen Allergy / Seasonal Allergic Rhinitis (SAR)1
2CompletedTreatmentPollen Allergy / Rhinoconjunctivitis / Seasonal Allergic Rhinitis (SAR)1
2CompletedTreatmentSeasonal Allergic Rhinitis (SAR)1
2, 3CompletedTreatmentCold Contact Urticaria1
3CompletedTreatmentChronic Urticaria1
3CompletedTreatmentPerennial Allergic Rhinitis (PAR)1
3CompletedTreatmentSeasonal Allergic Rhinitis (SAR)3
3CompletedTreatmentUrticarias1
4Active Not RecruitingTreatmentSeasonal Allergic Rhinitis (SAR)1
4CompletedSupportive CareAllergic Rhinitis (AR) / Urticarias1
4CompletedTreatmentAllergic Rhinitis (AR)1
4CompletedTreatmentAsthma Bronchial / Seasonal Allergic Rhinoconjunctivitis1
4CompletedTreatmentUrticarias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral20 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00203 mg/mLALOGPS
logP5.02ALOGPS
logP2.41ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)4.06ChemAxon
pKa (Strongest Basic)9.43ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area67.59 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity135.58 m3·mol-1ChemAxon
Polarizability54.96 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzimidazoles
Sub Class
Not Available
Direct Parent
Benzimidazoles
Alternative Parents
Phenylpropanes / Phenethylamines / Aralkylamines / Piperidines / N-substituted imidazoles / Heteroaromatic compounds / Trialkylamines / Amino acids / Azacyclic compounds / Carboxylic acids
show 6 more
Substituents
Benzimidazole / Phenylpropane / Phenethylamine / Aralkylamine / Monocyclic benzene moiety / N-substituted imidazole / Benzenoid / Piperidine / Azole / Imidazole
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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. Wang XY, Lim-Jurado M, Prepageran N, Tantilipikorn P, Wang de Y: Treatment of allergic rhinitis and urticaria: a review of the newest antihistamine drug bilastine. Ther Clin Risk Manag. 2016 Apr 13;12:585-97. doi: 10.2147/TCRM.S105189. eCollection 2016. [PubMed:27110120]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Efflux transmembrane transporter activity
Specific Function
Drug efflux transporter present in a number of stem cells that acts as a regulator of cellular differentiation. Able to mediate efflux from cells of the rhodamine dye and of the therapeutic drug do...
Gene Name
ABCB5
Uniprot ID
Q2M3G0
Uniprot Name
ATP-binding cassette sub-family B member 5
Molecular Weight
138639.48 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da

Drug created on May 06, 2016 12:33 / Updated on September 21, 2018 20:42