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Identification
NameFluticasone Propionate
Accession NumberDB00588  (APRD00065)
TypeSmall Molecule
GroupsApproved
Description

Fluticasone propionate, a medium-potency synthetic corticosteroid, is used topically to relieve inflammatory and pruritic symptoms of dermatoses and psoriasis, intranasally to manage symptoms of allergic and non-allergic rhinitis, and orally for the treatment of asthma. Fluticasone proprionate is marketed under several different brand names such as Flonase®. Fluticasone propionate is also available as a combination product of azelastine hydrochloride and fluticasone propionate called Dymista™. Dymista™ is indicated in patients over 12 years old for symptomatic relief of seasonal allergic rhinitis.

Structure
Thumb
Synonyms
SynonymLanguageCode
CutivateNot AvailableNot Available
FluticasonGermanINN
FluticasonaSpanishINN
FluticasoneFrenchINN
Fluticasone propionateNot AvailableNot Available
FluticasonumLatinINN
Salts
Name/CAS Structure Properties
Fluticasone Propionate
Thumb Not applicable DBSALT001035
Brand names
NameCompany
CutivateGlaxoSmithKline
EzicasIntas
FlixonaseGlaxoSmithKline
FlixotideGlaxoSmithKline
FlonaseGlaxoSmithKline
FloventGlaxoSmithKline
Flovent HFAGlaxoSmithKline
FLOVENTHFANot Available
FlunaseGlaxoSmithKline
NasofanTeva
PirinaseGlaxoSmithKline
SeretideGlaxoSmithKline
Brand mixtures
Brand NameIngredients
ADVAIRFluticasone Propionate + Salmeterol
ADVAIRDISKUSFluticasone Propionate + Salmeterol
DymistaAzelastine hydrochloride and Fluticasone propionate
FlixotideFluticasone and Salmeterol
FlixoventFluticasone and Salmeterol
Flosal DiskusFluticasone and Salmeterol
CategoriesNot Available
CAS number80474-14-2
WeightAverage: 500.571
Monoisotopic: 500.184429407
Chemical FormulaC25H31F3O5S
InChI KeyWMWTYOKRWGGJOA-CENSZEJFSA-N
InChI
InChI=1S/C25H31F3O5S/c1-5-20(31)33-25(21(32)34-12-26)13(2)8-15-16-10-18(27)17-9-14(29)6-7-22(17,3)24(16,28)19(30)11-23(15,25)4/h6-7,9,13,15-16,18-19,30H,5,8,10-12H2,1-4H3/t13-,15+,16+,18+,19+,22+,23+,24+,25+/m1/s1
IUPAC Name
(1R,2S,8S,10S,11S,13R,14R,15S,17S)-1,8-difluoro-14-{[(fluoromethyl)sulfanyl]carbonyl}-17-hydroxy-2,13,15-trimethyl-5-oxotetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-3,6-dien-14-yl propanoate
SMILES
[H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassSteroid Esters
Direct parentSteroid Esters
Alternative parentsAndrogens and Derivatives; Halogenated Steroids; Ketosteroids; Hydroxysteroids; Iridoids and Derivatives; Cyclohexanols; Thioesters; Carboxylic Acid Esters; Ketones; Fluorohydrins; Cyclic Alcohols and Derivatives; Thiocarboxylic Acid Esters; Ethers; Polyamines; Enolates; Organofluorides; Alkyl Fluorides
Substituents3-keto-steroid; 11-hydroxy-steroid; 9-halo-steroid; 6-halo-steroid; 11-noriridane monoterpene; monoterpene; cyclohexanol; cyclic alcohol; carboxylic-thioester; carboxylic acid ester; thiocarboxylic acid ester; halohydrin; fluorohydrin; ketone; secondary alcohol; enolate; carboxylic acid derivative; polyamine; thiocarboxylic acid derivative; ether; organohalogen; alcohol; organofluoride; carbonyl group; alkyl halide; alkyl fluoride
Classification descriptionThis compound belongs to the steroid esters. These are compounds containing a steroid moeity which bears a carboxylic acid ester group.
Pharmacology
IndicationFluticasone propionate, a medium-potency synthetic corticosteroid, is used topically to relieve inflammatory and pruritic symptoms of dermatoses and psoriasis, intranasally to manage symptoms of allergic and non-allergic rhinitis, and orally for the maintenance treatment of asthma as prophylactic therapy and for patients requiring oral corticosteroid therapy for asthma.
PharmacodynamicsFluticasone is an extremely potent vasoconstrictor and anti-inflammatory agent. Its effectiveness in inhaled forms is due to its direct local effect.
Mechanism of actionBinds to the glucocorticoid receptor. Unbound corticosteroids cross the membranes of cells such as mast cells and eosinophils, binding with high affinity to glucocorticoid receptors (GR). The results include alteration of transcription and protein synthesis, a decreased release of leukocytic acid hydrolases, reduction in fibroblast proliferation, prevention of macrophage accumulation at inflamed sites, reduction of collagen deposition, interference with leukocyte adhesion to the capillary wall, reduction of capillary membrane permeability and subsequent edema, reduction of complement components, inhibition of histamine and kinin release, and interference with the formation of scar tissue. In the management of asthma, the glucocorticoid receptor complexes down-regulates proinflammatory mediators such as interleukin-(IL)-1, 3, and 5, and up-regulates anti-inflammatory mediators such as IkappaB [inhibitory molecule for nuclear factor kappaB1], IL-10, and IL-12. The antiinflammatory actions of corticosteroids are also thought to involve inhibition of cytosolic phospholipase A2 (through activation of lipocortin-1 (annexin)) which controls the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.
AbsorptionThe extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Bioavailability, intranasal = <2%; Oral bioavailability is negligible and the major circulating entity is an inactive metabolite.
Volume of distribution

IV administration = 4.2 L/kg

Protein binding91%
Metabolism

Fluticasone propionate is metabolized in the liver by cytochrome P450 3A4-mediated hydrolysis of the 5-fluoromethyl carbothioate grouping. This transformation occurs in 1 metabolic step to produce the inactive 17-(beta)-carboxylic acid metabolite, the only known metabolite detected in man.

SubstrateEnzymesProduct
Fluticasone Propionate
fluticasone 17beta-carboxylic acidDetails
Route of eliminationLess than 5% of the oral dose was excreted in the urine as metabolites. The rest of the dose is excreted in the feces and parent drug and metabolites.
Half lifeTerminal elimination half-life = 7.8 hours
Clearance

The total blood clearance of fluticasone propionate is high (average, 1,093 mL/min), with renal clearance accounting for less than 0.02% of the total.

ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9964
Blood Brain Barrier + 0.9701
Caco-2 permeable + 0.5417
P-glycoprotein substrate Substrate 0.7099
P-glycoprotein inhibitor I Inhibitor 0.7192
P-glycoprotein inhibitor II Non-inhibitor 0.8636
Renal organic cation transporter Non-inhibitor 0.8689
CYP450 2C9 substrate Non-substrate 0.868
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.7407
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Inhibitor 0.8988
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8682
Ames test Non AMES toxic 0.798
Carcinogenicity Non-carcinogens 0.8901
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.3753 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.99
hERG inhibition (predictor II) Non-inhibitor 0.6125
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
  • Glaxo group ltd dba glaxosmithkline
  • Altana inc
  • G and w laboratories inc
  • Kv pharmaceutical co
  • Perrigo new york inc
  • Tolmar inc
  • Nycomed us inc
  • Taro pharmaceutical industries ltd
  • Apotex inc richmond hill
  • Hi tech pharmacal co inc
  • Roxane laboratories inc
Packagers
Dosage forms
FormRouteStrength
Aerosol, meteredRespiratory (inhalation)
CreamTopical
PowderRespiratory (inhalation)
Spray, meteredNasal
Spray, meteredNasalDYMISTA : 0.137MCG /SPRAY; 0.05MCG/SPRAY (AZELASTINE HYDROCHLORIDE; FLUTICASONE PROPIONATE)
Prices
Unit descriptionCostUnit
Fluticasone propionate powder1500.0USDg
Cutivate 0.05% Lotion 120ml Bottle454.6USDbottle
Advair Diskus 60 500-50 mcg/dose Aerosol Disp Pack328.14USDdisp
Advair Diskus 60 250-50 mcg/dose Aerosol Disp Pack249.48USDdisp
Flovent HFA 220 mcg/act Aerosol 12 gm Inhaler237.67USDinhaler
Cutivate 0.05% Cream 60 gm Tube217.11USDtube
Advair Diskus 60 100-50 mcg/dose Aerosol Disp Pack200.79USDdisp
Advair Diskus 14 500-50 mcg/dose Aerosol Disp Pack156.64USDdisp
Flovent HFA 110 mcg/act Aerosol 12 gm Inhaler153.01USDinhaler
Cutivate 0.005% Ointment 60 gm Tube128.28USDtube
Flovent HFA 44 mcg/act Aerosol 10.6 gm Inhaler114.27USDinhaler
Flovent Diskus 60 50 mcg/blist Aerosol Inhaler104.74USDinhaler
Flonase 50 mcg/act Suspension 16 gm Bottle94.59USDbottle
Fluticasone Propionate 50 mcg/act Suspension 16 gm Bottle78.28USDbottle
Cutivate 0.05% Cream 30 gm Tube62.99USDtube
Fluticasone Propionate 0.005% Ointment 60 gm Tube56.27USDtube
Fluticasone Propionate 0.05% Cream 60 gm Tube56.27USDtube
Cutivate 0.005% Ointment 30 gm Tube44.99USDtube
Fluticasone Propionate 0.005% Ointment 30 gm Tube35.67USDtube
Fluticasone Propionate 0.05% Cream 30 gm Tube35.67USDtube
Cutivate 0.005% Ointment 15 gm Tube32.99USDtube
Cutivate 0.05% Cream 15 gm Tube32.99USDtube
Advair hfa 230-21 mcg inhaler25.04USDg
Fluticasone Propionate 0.005% Ointment 15 gm Tube23.14USDtube
Fluticasone Propionate 0.05% Cream 15 gm Tube23.14USDtube
Advair hfa 115-21 mcg inhaler18.13USDg
Flovent hfa 220 mcg inhaler15.54USDg
Advair hfa 45-21 mcg inhaler14.59USDg
Flovent hfa 110 mcg inhaler12.26USDg
Flovent hfa 44 mcg inhaler10.99USDg
Flonase 0.05% nasal spray5.68USDg
Advair 500-50 diskus5.26USDeach
Advair 250-50 diskus4.0USDeach
Cutivate 0.05% cream3.48USDg
Advair 100-50 diskus3.22USDeach
Flovent 250 mcg diskus2.45USDeach
Flovent 100 mcg diskus1.83USDeach
Flovent 50 mcg diskus1.74USDeach
Flovent Diskus 500 mcg/dose Metered Inhalation Powder1.55USDdose
Flovent Diskus 250 mcg/dose Metered Inhalation Powder0.77USDdose
Flovent Hfa 250 mcg/dose Metered Dose Aerosol0.77USDdose
Flovent Hfa 125 mcg/dose Metered Dose Aerosol0.39USDdose
Flovent Hfa 50 mcg/dose Metered Dose Aerosol0.22USDdose
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Patents
CountryPatent NumberApprovedExpires (estimated)
United States75004442005-07-042025-07-04
United StatesRE400451993-09-072010-09-07
Canada23179992004-11-092020-09-11
Canada21256672000-03-132012-12-04
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point272-273 °CNot Available
water solubility0.51 mg/L (insoluble)Not Available
logP3.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0114ALOGPS
logP3.69ALOGPS
logP3.72ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)13.56ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area80.67 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity121.65 m3·mol-1ChemAxon
Polarizability49.26 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Joseph Kaspi, Oded Arad, Michael Brand, Moty Shookrun, Simona Malka, Mohammed Alnabari, Shalom Hazan, Vlado Malesevic, “Synthesis and powder preparation of fluticasone propionate.” U.S. Patent US20060009435, issued January 12, 2006.

US20060009435
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD01708
ChEBI31441
ChEMBLCHEMBL1473
Therapeutic Targets DatabaseDAP001039
PharmGKBPA449686
Drug Product Database2244293
RxListhttp://www.rxlist.com/cgi/generic2/cutivate.htm
Drugs.comhttp://www.drugs.com/cdi/fluticasone-furoate-spray.html
WikipediaFluticasone_propionate
ATC CodesD07AC17R01AD08R03BA05
AHFS Codes
  • 52:08.08
  • 84:06.00
  • 68:04.00
PDB EntriesNot Available
FDA labelshow(159 KB)
MSDSshow(39 KB)
Interactions
Drug Interactions
Drug
ConivaptanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Concurrent use of orally inhaled fluticasone with strong CYP3A4 inhibitors is not recommended.
CrizotinibConcurrent use with crizotinib may prolong QTc interval. Consider alternative therapy.
TelithromycinTelithromycin may reduce clearance of Fluticasone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Fluticasone if Telithromycin is initiated, discontinued or dose changed.
TipranavirTipranavir, co-administered with Ritonavir, may increase the plasma concentration of Fluticasone propionate. Concomitant therapy should be avoided if possible.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of fluticasone by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of fluticasone if voriconazole is initiated, discontinued or dose changed.
Food InteractionsNot Available

Targets

1. Glucocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Glucocorticoid receptor P04150 Details

References:

  1. Andersson O, Cassel TN, Gronneberg R, Bronnegard M, Stierna P, Nord M: In vivo modulation of glucocorticoid receptor mRNA by inhaled fluticasone propionate in bronchial mucosa and blood lymphocytes in subjects with mild asthma. J Allergy Clin Immunol. 1999 Apr;103(4):595-600. Pubmed
  2. Lumry WR: A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis. J Allergy Clin Immunol. 1999 Oct;104(4 Pt 1):S150-8. Pubmed
  3. Zhang X, Moilanen E, Kankaanranta H: Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophil apoptosis. Eur J Pharmacol. 2001 Nov 23;431(3):365-71. Pubmed
  4. Hogger P, Rohdewald P: Binding kinetics of fluticasone propionate to the human glucocorticoid receptor. Steroids. 1994 Oct;59(10):597-602. Pubmed
  5. Johnson M: Fluticasone propionate: safety profile. Cutis. 1996 Feb;57(2 Suppl):10-2. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Progesterone receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Progesterone receptor P06401 Details

References:

  1. Issar M, Sahasranaman S, Buchwald P, Hochhaus G: Differences in the glucocorticoid to progesterone receptor selectivity of inhaled glucocorticoids. Eur Respir J. 2006 Mar;27(3):511-6. Pubmed
  2. Austin RJ, Maschera B, Walker A, Fairbairn L, Meldrum E, Farrow SN, Uings IJ: Mometasone furoate is a less specific glucocorticoid than fluticasone propionate. Eur Respir J. 2002 Dec;20(6):1386-92. Pubmed

3. Cytosolic phospholipase A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytosolic phospholipase A2 P47712 Details

References:

  1. Sano A, Munoz NM, Sano H, Choi J, Zhu X, Jacobs B, Leff AR: Inhibition of cPLA2 translocation and leukotriene C4 secretion by fluticasone propionate in exogenously activated human eosinophils. Am J Respir Crit Care Med. 1999 Jun;159(6):1903-9. Pubmed
  2. Myo S, Zhu X, Myou S, Meliton AY, Liu J, Boetticher E, Lambertino AT, Xu C, Munoz NM, Leff AR: Additive blockade of beta 2-integrin adhesion of eosinophils by salmeterol and fluticasone propionate. Eur Respir J. 2004 Apr;23(4):511-7. Pubmed

4. Mineralocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Mineralocorticoid receptor P08235 Details

References:

  1. Austin RJ, Maschera B, Walker A, Fairbairn L, Meldrum E, Farrow SN, Uings IJ: Mometasone furoate is a less specific glucocorticoid than fluticasone propionate. Eur Respir J. 2002 Dec;20(6):1386-92. Pubmed
  2. Issar M, Sahasranaman S, Buchwald P, Hochhaus G: Differences in the glucocorticoid to progesterone receptor selectivity of inhaled glucocorticoids. Eur Respir J. 2006 Mar;27(3):511-6. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Pearce RE, Leeder JS, Kearns GL: Biotransformation of fluticasone: in vitro characterization. Drug Metab Dispos. 2006 Jun;34(6):1035-40. Epub 2006 Mar 24. Pubmed
  2. Murai T, Reilly CA, Ward RM, Yost GS: The inhaled glucocorticoid fluticasone propionate efficiently inactivates cytochrome P450 3A5, a predominant lung P450 enzyme. Chem Res Toxicol. 2010 Aug 16;23(8):1356-64. Pubmed

2. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Pearce RE, Leeder JS, Kearns GL: Biotransformation of fluticasone: in vitro characterization. Drug Metab Dispos. 2006 Jun;34(6):1035-40. Epub 2006 Mar 24. Pubmed
  2. Murai T, Reilly CA, Ward RM, Yost GS: The inhaled glucocorticoid fluticasone propionate efficiently inactivates cytochrome P450 3A5, a predominant lung P450 enzyme. Chem Res Toxicol. 2010 Aug 16;23(8):1356-64. Pubmed

3. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Pearce RE, Leeder JS, Kearns GL: Biotransformation of fluticasone: in vitro characterization. Drug Metab Dispos. 2006 Jun;34(6):1035-40. Epub 2006 Mar 24. Pubmed

Carriers

1. Corticosteroid-binding globulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Corticosteroid-binding globulin P08185 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11