Details of the Drug

General Information of Drug (ID: DMGCSVF)

• Drug Name: Fluticasone
• Synonyms: Fluticaps; Fluticaps (TN); Fluticasone (INN); S-(fluoromethyl) (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carbothioate

Indication

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[1]

• Therapeutic Class: Antiinflammatory Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 444.5
  Logarithm of the Partition Coefficient (xlogp); 3.2
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 8
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
  Bioavailability: The bioavailability of drug is 1.26% []
  Clearance: The clearance of drug is 57.8 L/h []
  Elimination: More than 90% of drug is eliminated in the feces and 1-2% in the urine []
  Half-life: The concentration or amount of drug in body reduced by one-half in 14.0 hours []
  Metabolism: The drug is metabolized via the hepatic []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 6.65226 micromolar/kg/day [3]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.1% [4]
  Vd: The volume of distribution (Vd) of drug is 4.2 L/kg []
  Water Solubility: The ability of drug to dissolve in water is measured as 0.00051 mg/mL [2]
• Chemical Identifiers:
  Formula: C22H27F3O4S
  IUPAC Name: S-(fluoromethyl) (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carbothioate
  Canonical SMILES: C[C@@H]1C[C@H]2[C@@H]3C[C@@H](C4=CC(=O)C=C[C@@]4([C@]3([C@H](C[C@@]2([C@]1(C(=O)SCF)O)C)O)F)C)F
  InChI: InChI=1S/C22H27F3O4S/c1-11-6-13-14-8-16(24)15-7-12(26)4-5-19(15,2)21(14,25)17(27)9-20(13,3)22(11,29)18(28)30-10-23/h4-5,7,11,13-14,16-17,27,29H,6,8-10H2,1-3H3/t11-,13+,14+,16+,17+,19+,20+,21+,22+/m1/s1
  InChIKey: MGNNYOODZCAHBA-GQKYHHCASA-N
• Cross-matching ID:
  PubChem CID: 5311101
  ChEBI ID: CHEBI:5134
  CAS Number: 90566-53-3
  DrugBank ID: DB13867
  TTD ID: D0LC6K
  INTEDE ID: DR0735

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Antagonist	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[6]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Substrate	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Allergic rhinitis
• ICD Disease Classification: CA08.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	5.82E-01	-6.00E-02	-2.69E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	9.85E-01	2.24E-02	7.33E-02

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Fluticasone (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Fluticasone caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[8]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Fluticasone caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[8]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Fluticasone caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[8]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] BDDCS applied to over 900 drugs
• [3] 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
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Fluticasone furoate nasal spray in allergic rhinitis. Drugs Today (Barc). 2008 Apr;44(4):251-60.
• [6] Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab Rev. 2010 Nov;42(4):621-35.
• [7] Biotransformation of fluticasone: in vitro characterization. Drug Metab Dispos. 2006 Jun;34(6):1035-40.
• [8] Cerner Multum, Inc. "Australian Product Information.".