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Identification
Name Fluticasone Propionate
Accession Number DB00588 (APRD00065)
Type small molecule
Groups approved
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.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Advair Diskus
Cutivate
Flixonase
Flixotide
Flonase
Flovent
Flovent HFA
Flunase
Brand mixtures Not Available
Categories
  • Anti-inflammatory Agents
  • Adrenergic Agents
  • Dermatologic Agents
  • Bronchodilator Agents
  • Anti-Allergic Agents
CAS number 80474-14-2
Weight Average: 500.571
Monoisotopic: 500.184429407
Chemical Formula C25H31F3O5S
InChI Key InChIKey=WMWTYOKRWGGJOA-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
Plain Text
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[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-dien-14-yl propanoate
SMILES
CCC(=O)O[C@@]1([C@H](C)C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]12C)C(=O)SCF
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Alkyl Halides
  • Ethers
  • Esters
  • Alcohols and Polyols
  • Ketones
Pharmacology
Indication For the maintenance treatment of asthma as prophylactic therapy and for patients requiring oral corticosteroid therapy for asthma.
Pharmacodynamics 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.
Mechanism of action Binds 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.
Absorption The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier.
Volume of distribution
  • 2.3 to 16.7 L/kg
Protein binding 91%
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.
Route of elimination Not Available
Half life 10 hours
Clearance
  • 1093 mL/min
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
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
Form Route Strength
Aerosol, metered Respiratory (inhalation)
Cream Topical
Powder Respiratory (inhalation)
Spray, metered Nasal
Prices
Unit description Cost Unit
Fluticasone propionate powder 1500.0 USD g
Cutivate 0.05% Lotion 120ml Bottle 454.6 USD bottle
Advair Diskus 60 500-50 mcg/dose Aerosol Disp Pack 328.14 USD disp
Advair Diskus 60 250-50 mcg/dose Aerosol Disp Pack 249.48 USD disp
Flovent HFA 220 mcg/act Aerosol 12 gm Inhaler 237.67 USD inhaler
Cutivate 0.05% Cream 60 gm Tube 217.11 USD tube
Advair Diskus 60 100-50 mcg/dose Aerosol Disp Pack 200.79 USD disp
Advair Diskus 14 500-50 mcg/dose Aerosol Disp Pack 156.64 USD disp
Flovent HFA 110 mcg/act Aerosol 12 gm Inhaler 153.01 USD inhaler
Cutivate 0.005% Ointment 60 gm Tube 128.28 USD tube
Flovent HFA 44 mcg/act Aerosol 10.6 gm Inhaler 114.27 USD inhaler
Flovent Diskus 60 50 mcg/blist Aerosol Inhaler 104.74 USD inhaler
Flonase 50 mcg/act Suspension 16 gm Bottle 94.59 USD bottle
Fluticasone Propionate 50 mcg/act Suspension 16 gm Bottle 78.28 USD bottle
Cutivate 0.05% Cream 30 gm Tube 62.99 USD tube
Fluticasone Propionate 0.005% Ointment 60 gm Tube 56.27 USD tube
Fluticasone Propionate 0.05% Cream 60 gm Tube 56.27 USD tube
Cutivate 0.005% Ointment 30 gm Tube 44.99 USD tube
Fluticasone Propionate 0.005% Ointment 30 gm Tube 35.67 USD tube
Fluticasone Propionate 0.05% Cream 30 gm Tube 35.67 USD tube
Cutivate 0.005% Ointment 15 gm Tube 32.99 USD tube
Cutivate 0.05% Cream 15 gm Tube 32.99 USD tube
Advair hfa 230-21 mcg inhaler 25.04 USD g
Fluticasone Propionate 0.005% Ointment 15 gm Tube 23.14 USD tube
Fluticasone Propionate 0.05% Cream 15 gm Tube 23.14 USD tube
Advair hfa 115-21 mcg inhaler 18.13 USD g
Flovent hfa 220 mcg inhaler 15.54 USD g
Advair hfa 45-21 mcg inhaler 14.59 USD g
Flovent hfa 110 mcg inhaler 12.26 USD g
Flovent hfa 44 mcg inhaler 10.99 USD g
Flonase 0.05% nasal spray 5.68 USD g
Advair 500-50 diskus 5.26 USD each
Advair 250-50 diskus 4.0 USD each
Cutivate 0.05% cream 3.48 USD g
Advair 100-50 diskus 3.22 USD each
Flovent 250 mcg diskus 2.45 USD each
Flovent 100 mcg diskus 1.83 USD each
Flovent 50 mcg diskus 1.74 USD each
Flovent Diskus 500 mcg/dose Metered Inhalation Powder 1.55 USD dose
Flovent Diskus 250 mcg/dose Metered Inhalation Powder 0.77 USD dose
Flovent Hfa 250 mcg/dose Metered Dose Aerosol 0.77 USD dose
Flovent Hfa 125 mcg/dose Metered Dose Aerosol 0.39 USD dose
Flovent Hfa 50 mcg/dose Metered Dose Aerosol 0.22 USD dose
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Patents
Country Patent Number Approved Expires (estimated)
United States 7500444 2005-07-04 2025-07-04
United States RE40045 1993-09-07 2010-09-07
Canada 2317999 2004-11-09 2020-09-11
Canada 2125667 2000-03-13 2012-12-04
Properties
State solid
Melting point 272-273 oC
Experimental Properties
Property Value Source
water solubility 0.51 mg/L (insoluble) PhysProp
logP 3.4 PhysProp
Predicted Properties
Property Value Source
water solubility 1.14e-02 g/l ALOGPS
logP 3.69 ALOGPS
logP 3.72 ChemAxon Molconvert
logS -4.6 ALOGPS
pKa 14.48 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 80.67 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 121.65 ChemAxon Molconvert
polarizability 48.94 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D01708 Link_out
PubChem Compound 444036 Link_out
PubChem Substance 46506140 Link_out
ChemSpider 392059 Link_out
ChEBI 31441 Link_out
ChEMBL 31441 Link_out
Therapeutic Targets Database DAP001039 Link_out
PharmGKB PA449687 Link_out
Drug Product Database 2244293 Link_out
RxList http://www.rxlist.com/cgi/generic2/cutivate.htm Link_out
Drugs.com http://www.drugs.com/cdi/fluticasone-furoate-spray.html Link_out
ATC Codes
  • D07AC17
  • R01AD08
  • R03BA05
AHFS Codes
  • 52:08.08
  • 84:06.00
  • 68:04.00
PDB Entries Not Available
FDA label show (159 KB)
MSDS show (39 KB)
Interactions
Drug Interactions
Drug Interaction
Conivaptan CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Concurrent use of orally inhaled fluticasone with strong CYP3A4 inhibitors is not recommended.
Telithromycin Telithromycin 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.
Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Fluticasone propionate. Concomitant therapy should be avoided if possible.
Voriconazole Voriconazole, 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 Interactions Not Available
Targets

1. Glucocorticoid receptor

Pharmacological action: yes
Actions: agonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth

Organism class: human
UniProt ID: P04150 Link_out
Gene: NR3C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: agonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues

Organism class: human
UniProt ID: P06401 Link_out
Gene: PGR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: inhibitor

Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response

Organism class: human
UniProt ID: P47712 Link_out
Gene: PLA2G4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: antagonist

Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels

Organism class: human
UniProt ID: P08235 Link_out
Gene: NR3C2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species

UniProt ID: P08185 Link_out
Gene: SERPINA6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Drug created on June 13, 2005 07:24 / Updated on April 22, 2012 10:17