Details of the Drug

General Information of Drug (ID: DMJKROX)

• Drug Name: Luvox
• Synonyms: FLUVOXAMINE MALEATE; 61718-82-9; Fevarin; Luvox CR; Fluvoxamine (maleate); UNII-5LGN83G74V; DU23000; DU-23000; SME 3110; 5LGN83G74V; MK-264; 54739-18-3; 5-Methoxy-4'-trifluoromethylvalerophenone (E)-O-2-aminoethyloxime monomaleate; 5-Methoxy-4'-(trifluoromethyl)valerophenone (E)-O-(2-aminoethyl)oxime, maleate (1:1); 54739-20-7; 1-Pentanone, 5-methoxy-1-(4-(trifluoromethyl)phenyl)-, O-(2-aminoethyl)oxime, (E)-, (Z)-2-butenedioate (1:1); C19H25F3N2O6

Indication

Disease Entry	ICD 11	Status	REF
Anxiety disorder	6B00-6B0Z	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight; 434.4
  Logarithm of the Partition Coefficient; Not Available
  Rotatable Bond Count; 11
  Hydrogen Bond Donor Count; 3
  Hydrogen Bond Acceptor Count; 11
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 31.95 mL/min/kg [3]
  Elimination: 2% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 12.5 hours [3]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 13.4627 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.2% [3]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 23.5 L/kg [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 14.869 mg/mL [2]
• Chemical Identifiers:
  Formula: C19H25F3N2O6
  IUPAC Name: (Z)-but-2-enedioic acid;2-[(E)-[5-methoxy-1-[4-(trifluoromethyl)phenyl]pentylidene]amino]oxyethanamine
  Canonical SMILES: COCCCC/C(=N\\OCCN)/C1=CC=C(C=C1)C(F)(F)F.C(=C\\C(=O)O)\\C(=O)O
  InChI: InChI=1S/C15H21F3N2O2.C4H4O4/c1-21-10-3-2-4-14(20-22-11-9-19)12-5-7-13(8-6-12)15(16,17)18;5-3(6)1-2-4(7)8/h5-8H,2-4,9-11,19H2,1H3;1-2H,(H,5,6)(H,7,8)/b20-14+;2-1-
  InChIKey: LFMYNZPAVPMEGP-PIDGMYBPSA-N
• Cross-matching ID:
  PubChem CID: 9560989
  ChEBI ID: CHEMBL1409
  CAS Number: 61718-82-9
  TTD ID: D0M5JI
  INTEDE ID: DR0740
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug ADMET Endpoint Profile (DAE)NEW: Click to Jump to the Detailed DAE Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Modulator	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Substrate	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[8]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
5-hydroxytryptamine receptor 2A (HTR2A)	OTWXJX0M	5HT2A_HUMAN	Drug Response	[9]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[10]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Gene/Protein Processing	[11]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Gene/Protein Processing	[12]
Vasopressin-neurophysin 2-copeptin (AVP)	OTAVZ76K	NEU2_HUMAN	Gene/Protein Processing	[13]

Molecular Expression Atlas of This Drug

• The Studied Disease: Anxiety disorder
• ICD Disease Classification: 6B00-6B0Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Serotonin transporter (SERT)	DTT	SLC6A4	8.76E-01	7.18E-05	6.19E-04
Cytochrome P450 2E1 (CYP2E1)	DME	CYP2E1	9.45E-02	-1.86E-01	-9.83E-01
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	8.46E-01	-6.63E-03	-4.49E-02
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	8.70E-01	2.98E-02	1.22E-01

References

• [1] ClinicalTrials.gov (NCT00743834) Cost-Effectiveness of Adding Web-Based Cognitive-Behavioral Therapy (CBT) to Luvox CR for Obsessive Compulsive Disorder (OCD). U.S. National Institutes of Health.
• [2] BDDCS applied to over 900 drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] 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
• [5] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [6] Antidepressant drugs in the elderly--role of the cytochrome P450 2D6. World J Biol Psychiatry. 2003 Apr;4(2):74-80.
• [7] Is therapeutic drug monitoring a case for optimizing clinical outcome and avoiding interactions of the selective serotonin reuptake inhibitors? Ther Drug Monit. 2000 Apr;22(2):143-54.
• [8] Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide. Clin Pharmacokinet. 2007;46(7):613-22.
• [9] [Serotonin 2A receptor gene polymorphism and clinical efficacy of fluvoxamine in children with autistic disorder]. No To Hattatsu. 2003 Jan;35(1):23-8.
• [10] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [11] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [12] Brugada syndrome ECG provoked by the selective serotonin reuptake inhibitor fluvoxamine. Europace. 2010 Feb;12(2):282-3. doi: 10.1093/europace/eup332. Epub 2009 Oct 29.
• [13] [Three cases of severe hyponatremia under taking selective serotonin reuptake inhibitor (SSRI)]. Nihon Jinzo Gakkai Shi. 2000 Oct;42(8):644-8.