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], [2]

• Therapeutic Class: Antiallergic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 381.9
  Topological Polar Surface Area (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: CHEBI:2950
  CAS Number: 58581-89-8
  DrugBank ID: DB00972
  TTD ID: D00JVR
  VARIDT ID: DR00483
  INTEDE ID: DR0165

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], [11]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[12]
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[13]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[14]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[12]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Substrate	[14]
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[14]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[14]

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

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]	[82]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Azelastine and Esketamine.	Depression [6A70-6A7Z]	[83]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Azelastine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[84]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Azelastine and Lasmiditan.	Migraine [8A80]	[83]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Azelastine and Flibanserin.	Mood disorder [6A60-6E23]	[83]
Thalidomide	DM70BU5	Moderate	Additive CNS depression effects by the combination of Azelastine and Thalidomide.	Multiple myeloma [2A83]	[83]

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