Details of the Drug

General Information of Drug (ID: DMXTMBJ)

Drug Name
Azelastine
Synonyms
Azelastina; Azelastinum; Optivar; Astelin (TN); Astepro (TN); Azelastina [INN-Spanish]; Azelastine (INN); Azelastine [INN:BAN]; Azelastinum [INN-Latin]; Optivar (TN); 4-((4-Chlorophenyl)methyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthalazinone hydrochloride; 4-((4-chlorophenyl)methyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthalazinone HCl; 4-(4-chlorobenzyl)-2-(1-methylazepan-4-yl)phthalazin-1(2H)-one; 4-(p-Chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-phthalazinone; 4-(p-chlorobenzyl)-2-(N-methylperhydroazepinyl-(4))-1-(2H)-phthalazinone; 4-[(4-chlorophenyl)methyl]-2-(1-methylazepan-4-yl)phthalazin-1(2H)-one; 4-[(4-chlorophenyl)methyl]-2-(1-methylazepan-4-yl)phthalazin-1-one
Indication
Disease Entry ICD 11 Status REF
Allergic conjunctivitis 9A60.02 Approved [1]
Allergic rhinitis CA08.0 Approved [2]
Seasonal allergic rhinitis CA08.01 Approved [2]
Vasomotor/allergic rhinitis CA08 Approved [2]
Therapeutic Class
Antiallergic Agents
Affected Organisms
Humans and other mammals
ATC Code
R01AC03: Azelastine
R01AC: Antiallergic agents, excl. corticosteroids
R01A: DECONGESTANTS AND OTHER NASAL PREPARATIONS FOR TOPICAL USE
R01: NASAL PREPARATIONS
R: RESPIRATORY SYSTEM
R06AX19: Azelastine
R06AX: Other antihistamines for systemic use
R06A: ANTIHISTAMINES FOR SYSTEMIC USE
R06: ANTIHISTAMINES FOR SYSTEMIC USE
R: RESPIRATORY SYSTEM
S01GX07: Azelastine
S01GX: Other antiallergics
S01G: DECONGESTANTS AND ANTIALLERGICS
S01: OPHTHALMOLOGICALS
S: SENSORY ORGANS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 381.9
Logarithm of the Partition Coefficient (xlogp) 4.4
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2-3 h [3]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [4]
Bioavailability
99% of drug becomes completely available to its intended biological destination(s) [5]
Clearance
The clearance of drug is 0.5 L/h/kg [6]
Elimination
Approximately 75% of the oral dose was excreted in the feces, with less than 10% as unchanged form [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 22 hours [3]
Metabolism
The drug is metabolized via the cytochrome P450 enzyme system [7]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.2985 micromolar/kg/day [8]
Unbound Fraction
The unbound fraction of drug in plasma is 0.17% [9]
Vd
The volume of distribution (Vd) of drug is 14.5 L/kg [3]
Chemical Identifiers
Formula
C22H24ClN3O
IUPAC Name
4-[(4-chlorophenyl)methyl]-2-(1-methylazepan-4-yl)phthalazin-1-one
Canonical SMILES
CN1CCCC(CC1)N2C(=O)C3=CC=CC=C3C(=N2)CC4=CC=C(C=C4)Cl
InChI
InChI=1S/C22H24ClN3O/c1-25-13-4-5-18(12-14-25)26-22(27)20-7-3-2-6-19(20)21(24-26)15-16-8-10-17(23)11-9-16/h2-3,6-11,18H,4-5,12-15H2,1H3
InChIKey
MBUVEWMHONZEQD-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
2267
ChEBI ID
CHEMBL639
CAS Number
58581-89-8
UNII
ZQI909440X
DrugBank ID
DB00972
TTD ID
D00JVR
VARIDT ID
DR00483
INTEDE ID
DR0165
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Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Histamine H1 receptor (H1R) TTTIBOJ HRH1_HUMAN Antagonist [10]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [11]
Cytochrome P450 2D6 (CYP2D6)
Main DME 		DECB0K3 CP2D6_HUMAN Substrate [12]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [13]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [11]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Substrate [13]
Cytochrome P450 1A2 (CYP1A2)
Main DME 		DEJGDUW CP1A2_HUMAN Substrate [11]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [13]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [13]
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Molecular Expression Atlas of This Drug

The Studied Disease Allergic conjunctivitis
ICD Disease Classification 9A60.02
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Histamine H1 receptor (H1R) DTT HRH1 6.74E-01 0.13 0.43
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 5.57E-01 -7.89E-02 -7.93E-01
Cytochrome P450 2A6 (CYP2A6) DME CYP2A6 8.99E-01 4.59E-03 2.19E-02
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 8.46E-01 -6.63E-03 -4.49E-02
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 9.57E-01 9.43E-03 1.29E-01
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 9.62E-01 2.57E-02 1.10E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 8.70E-01 2.98E-02 1.22E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 2.35E-01 2.78E-02 2.09E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.76E-01 1.26E-01 8.27E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Azelastine (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Tucatinib DMBESUA Moderate Decreased metabolism of Azelastine caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [14]
Esketamine DMVU687 Moderate Additive CNS depression effects by the combination of Azelastine and Esketamine. Depression [6A70-6A7Z] [15]
Allopregnanolone DMNLHAC Moderate Additive CNS depression effects by the combination of Azelastine and Allopregnanolone. Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z] [16]
Lasmiditan DMXLVDT Moderate Additive CNS depression effects by the combination of Azelastine and Lasmiditan. Migraine [8A80] [15]
Flibanserin DM70DTN Moderate Additive CNS depression effects by the combination of Azelastine and Flibanserin. Mood disorder [6A60-6E23] [15]
Thalidomide DM70BU5 Moderate Additive CNS depression effects by the combination of Azelastine and Thalidomide. Multiple myeloma [2A83] [15]
⏷ Show the Full List of 6 DDI Information of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7121).
2 Azelastine FDA Label
3 Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007 Oct;23(10):2441-52.
4 BDDCS applied to over 900 drugs
5 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
6 FDA Approved Drug Product: Azelastine nasal spray
7 Jensen L, Kupcova V, Arold G, Pettersson J, Hjerpsted JB: Pharmacokinetics and tolerability of semaglutide in people with hepatic impairment. Diabetes Obes Metab. 2018 Apr;20(4):998-1005. doi: 10.1111/dom.13186. Epub 2018 Jan 17.
8 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
9 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
10 Intact cell binding for in vitro prediction of sedative and non-sedative histamine H1-receptor antagonists based on receptor internalization. J Pharmacol Sci. 2008 May;107(1):66-79.
11 In vitro identification of the human cytochrome P-450 enzymes involved in the N-demethylation of azelastine. Drug Metab Dispos. 1999 Aug;27(8):942-6.
12 Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Jul;27(7):792-7.
13 Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91.
14 Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
15 Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
16 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.