ALCAFTADINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H21N3O
Molecular Weight	307.3895
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCC(CC1)=C2C3=NC=C(C=O)N3CCC4=C2C=CC=C4

InChI

InChIKey=MWTBKTRZPHJQLH-UHFFFAOYSA-N

InChI=1S/C19H21N3O/c1-21-9-6-15(7-10-21)18-17-5-3-2-4-14(17)8-11-22-16(13-23)12-20-19(18)22/h2-5,12-13H,6-11H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22348913 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022134s004lbl.pdf

Alcaftadine is a broad-spectrum antihistamine displaying a high affinity for histamine H1 and H2 receptors and a lower affinity for H4 receptors. It also exhibits modulatory action on immune cell recruitment and mast cell stabilizing effects. Alcaftadine is an inhibitor of the release of histamine from mast cells. Decreased chemotaxis and inhibition of eosinophil activation has also been demonstrated. LASTACAFT® (alcaftadine ophthalmic solution) indicated for the prevention of itching associated with allergic conjunctivitis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22348913	Antagonist 2778	3.1 nM [Ki]
Histamine H2 receptor 46 Target ID: CHEMBL1941 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22348913	Antagonist 2778	58.0 nM [Ki]
Histamine H4 receptor 20 Target ID: CHEMBL3759 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22348913	Antagonist 2778	2.9 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Itching associated with allergic conjunctivitis 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022134s004lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/26185412	Preventing		Approved 8429	LASTACAFT Approved Use LASTACAFT® is an H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis. LASTACAFT® is an H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis. Launch Date 2010

C_max

Value	Dose	Co-administered	Analyte	Population
0.05 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21314437/	1 drop single, intraocular dose: 1 drop route of administration: Intraocular experiment type: SINGLE co-administered:		ALCAFTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
0.04 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21314437/	1 drop single, intraocular dose: 1 drop route of administration: Intraocular experiment type: SINGLE co-administered:		ALCAFTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21314437/	1 drop single, intraocular dose: 1 drop route of administration: Intraocular experiment type: SINGLE co-administered:		ALCAFTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
60.8% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21314437/	1 drop single, intraocular dose: 1 drop route of administration: Intraocular experiment type: SINGLE co-administered:		ALCAFTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 drop 1 times / week multiple, ophthalmic Recommended Dose: 1 drop, 1 times / week Route: ophthalmic Route: multiple Dose: 1 drop, 1 times / week Sources: https://clinicaltrials.gov/ct2/show/NCT00889330	unhealthy, 37.8 n = 30 Health Status: unhealthy Condition: Allergic Conjunctivitis Age Group: 37.8 Sex: M+F Population Size: 30 Sources: https://clinicaltrials.gov/ct2/show/NCT00889330	Sources: https://clinicaltrials.gov/ct2/show/NCT00889330

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C8 911 CYP2E1 882 CYP4A 19	CYP1A2 1054 CYP2A6 543 CYP2C8 693 CYP2C19 991 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=47; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=47; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=47; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=47; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=47; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=47; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	no
CYP4A 33	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=47; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	no

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=46; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	likely
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=46; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=46; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=46; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	no
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=46; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	unlikely
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=46; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	unlikely
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=46; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 23-26	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=46; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=15; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 15, 23-26	yes	no (co-administration study) Comment: Human liver microsomes (10 donors/patients); Following 2 mg oral dose of alcaftadine, co-administered ketoconazole (a CYP3A4 inhibitor) was found not to inhibit the in vivo metabolism of alcaftadine as there was no changes in the plasma concentrations of alcaftadine and the AUC of the metabolite R90692 increased 10% following co-administration of ketoconazole. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=46; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=15; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000clinpharm.pdf#page=25 Page: 46-48, (ClinPharm) 15, 23-26

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022134s000PharmR.pdf#page=19 Page: 19.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:71023	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:71023
ChemicalBook	CB21011726	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB21011726
MolPort	MolPort-023-219-144	https://www.molport.com/shop/molecule-link/MolPort-023-219-144
ZINC	ZINC000011726211	http://zinc15.docking.org/substances/ZINC000011726211

PubMed

Title	Date	PubMed
Histamine and H1-antihistamines: celebrating a century of progress.	2011 Dec	22035879
Vilazodone hydrochloride, linagliptin, and alcaftadine.	2011 Jul-Aug	21752782
Alcaftadine for the prevention of itching associated with allergic conjunctivitis.	2012 Jul-Aug	22811343

Patents

Sample Use Guides

In Vivo Use Guide

Instill one drop in each eye once daily. Ophthalmic solution containing alcaftadine, 0.25% (2.5 mg/mL).

Route of Administration: Other

In Vitro Use Guide

Unknown

Name

Type

Language

ALCAFTADINE

Official Name

English

ALCAFTADINE [VANDF]

Common Name

English

ALCAFTADINE [USAN]

Common Name

English

LASTACAFT

Brand Name

English

R 89674

Code

English

Alcaftadine [WHO-DD]

Common Name

English

ALCAFTADINE [JAN]

Common Name

English

ALCAFTADINE [MART.]

Common Name

English

11-(1-Methylpiperidin-4-ylidene)-6,11-dihydro-5H-imidazolo[2,1-b][3]benzazepine-3-carbaldehyde

Systematic Name

English

5H-IMIDAZO(2,1-B)(3)BENZAZEPINE-3-CARBOXALDEHYDE, 6,11-DIHYDRO-11-(1-METHYL-4-PIPERIDINYLIDENE)-

Systematic Name

English

R-89674

Code

English

ALCAFTADINE [ORANGE BOOK]

Common Name

English

4-(1-METHYL-PIPERIDIN-4-YLIDENE)-9,10-DIHYDRO-4H-3,10A-DIAZA-BENZO(F)AZULENE-1-CARBALDEHYDE

Common Name

English

alcaftadine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C257