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
Affected Organisms
Humans and other mammals
ATC Code
D07AC17: Fluticasone
D07AC: Corticosteroids, potent (group III)
D07A: CORTICOSTEROIDS, PLAIN
D07: CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS
D: DERMATOLOGICALS
R01AD08: Fluticasone
R01AD: Corticosteroids
R01A: DECONGESTANTS AND OTHER NASAL PREPARATIONS FOR TOPICAL USE
R01: NASAL PREPARATIONS
R: RESPIRATORY SYSTEM
R03BA05: Fluticasone
R03BA: Glucocorticoids
R03B: OTHER DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES, INHALANTS
R03: DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R: RESPIRATORY SYSTEM
R03BA05: Fluticasone
R03BA: Glucocorticoids
R03B: OTHER DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES, INHALANTS
R03: DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R: RESPIRATORY SYSTEM
R03BA05: Fluticasone
R03BA: Glucocorticoids
R03B: OTHER DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES, INHALANTS
R03: DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R: RESPIRATORY SYSTEM
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#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
UNII
CUT2W21N7U
DrugBank ID
DB13867
TTD ID
D0LC6K
INTEDE ID
DR0735
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

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 Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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
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 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.".