Fluticasone Propionate - C25h31f3o5s - Pubchem

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PUBCHEM COMPOUND FLUTICASONE PROPIONATE
FLUTICASONE PROPIONATE
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Drug Information
Pharmacology
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Cite this Record
Bioactivities
444036
FLUTICASONE PROPIONATE; Cutivate; Flonase; Flovent;
Chemical Names:
Flixonase; Flixotide; More...
Molecular Formula:
C25H31F3O5S
Molecular Weight:
500.57085 g/mol
InChI Key:
WMWTYOKRWGGJOA-CENSZEJFSA-N
UNII:
O2GMZ0LF5W
Modify Date:
2015-10-31
Create Date:
2005-06-24
Fluticasone Propionate is the propionate salt form of fluticasone, a synthetic trifluorinated glucocorticoid
receptor agonist with antiallergic, antiinflammatory and antipruritic effects. Binding and activation of the
glucocorticoid receptor results in the activation of lipocortin that in turn inhibits cytosolic phospholipase A2,
which triggers cascade of reactions involved in synthesis of inflammatory mediators, such as prostaglandins and
leukotrienes. Secondly, mitogen-activated protein kinase (MAPK) phosphatase 1 is induced, thereby leads to
dephosphorylation and inactivation of Jun N-terminal kinase directly inhibiting c-Jun mediated transcription.
Finally, transcriptional activity of nuclear factor (NF)-kappa-B is blocked, thereby inhibits the transcription of
cyclooxygenase 2, which is essential for prostaglandin production.
Pharmacology from NCIt
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(TM). Dymista(TM) is indicated in patients over 12 years
old for symptomatic relief of seasonal allergic rhinitis.
from DrugBank
Contents
1 2D Structure
2 3D Conformer
3 Names and Identifiers
4 Chemical and Physical Properties
5 Related Records
6 Chemical Vendors
7 Drug and Medication Information
8 Pharmacology and Biochemistry
9 Use and Manufacturing
10 Identification
11 Safety and Hazards
12 Toxicity
13 Literature
14 Patents
15 Biomolecular Interactions and Pathways
16 Biological Test Results
17 Classification
18 Information Sources
1 2D Structure
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from PubChem
2 3D Conformer
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from PubChem
3 Names and Identifiers

3.1 Computed Descriptors
3.1.1 IUPAC Name
[(6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-17-(fluoromethylsulfanylcarbonyl)-11-hydroxy-10,13,16trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] propanoate
from PubChem
3.1.2 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)6-722(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
from PubChem
3.1.3 InChI Key

WMWTYOKRWGGJOA-CENSZEJFSA-N
from PubChem
3.1.4 Canonical SMILES

CCC(=O)OC1(C(CC2C1(CC(C3(C2CC(C4=CC(=O)C=CC43C)F)F)O)C)C)C(=O)SCF
from PubChem
3.1.5 Isomeric SMILES

CCC(=O)O[C@@]1([C@@H](C[C@@H]2[C@@]1(C[C@@H]([C@]3([C@H]2C[C@@H]
(C4=CC(=O)C=C[C@@]43C)F)F)O)C)C)C(=O)SCF
from PubChem
3.2 Other Identifiers

3.2.1 CAS
80474-14-2
from DrugBank
3.2.2 EC Number
617-082-4
from ECHA
3.2.3 UNII
O2GMZ0LF5W
from FDA/SPL Indexing data
3.3 Synonyms
3.3.1 MeSH Synonyms
1. Cutivate
2. Flixonase
3. Flixotide
4. Flonase
5. Flovent
6. fluticasone
7. fluticasone propionate
from MeSH
3.3.2 Depositor-Supplied Synonyms

1. FLUTICASONE PROPIONATE
11. Fluspiral
21. Inalacor
31. Cutivate (TN)
2. Cutivate
12. Flutide
22. Rinosone
32. Flixonase Nasal Spray
3. Flonase
13. Flovent Diskus 50
23. Trialona
33. 80474-14-2
4. Flovent
24. Ubizol
34. CCI-18781
5. Flixonase
25. Zoflut
35. Fluxonal
6. Flixotide
16. Asmatil
26. Flixotide Disks
36. Skyron
7. Flovent HFA
17. Axotide
27. Flixotide Disk
37. Fluticasonpropionat Allen
8. Flunase
18. Brethal
28. Flovent Diskus
38. Flonase (TN)
9. atemur
19. Fluinol
29. Flonase Aq
39. Flovent (TN)
20. Flutivate
30. Flixotide Inhaler
40. CHEBI:31441
10. Flusonal
from PubChem
4 Chemical and Physical Properties

4.1 Computed Properties
Molecular Weight
500.57085 g/mol
Molecular Formula
C25H31F3O5S
XLogP3
Hydrogen Bond Donor Count
Hydrogen Bond Acceptor Count
Rotatable Bond Count
Exact Mass
500.18443 g/mol
Monoisotopic Mass
500.18443 g/mol
Topological Polar Surface Area
106 A^2
Heavy Atom Count
34
Formal Charge
Complexity
984
Isotope Atom Count
Defined Atom Stereocenter Count
Undefined Atom Stereocenter Count
Defined Bond Stereocenter Count
Undefined Bond Stereocenter Count
Covalently-Bonded Unit Count
1
from PubChem
4.2 Experimental Properties

4.2.1 Melting Point
272-273 C
from DrugBank
4.2.2 Solubility
In water, 102 mg/L at 25 deg C (est)
US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from, as of April 23, 2009:
http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
from HSDB
Water Solubility
0.51 mg/L (insoluble)
from DrugBank
4.2.3 Vapor Pressure

7.45X10-13 mm Hg at 25 deg C (est)
from HSDB
4.2.4 LogP
log Kow = 1.40 (est)
from HSDB
3.4
from DrugBank
4.3 Crystal Structures

Crystal Structures: 1 of 2
CCDC Number
735705
Crystal Structure Data
DOI:10.5517/ccspkff
Associated Article
DOI:10.1039/a904702f
from The Cambridge Structural Database
Crystal Structures: 2 of 2
CCDC Number
290181
Crystal Structure Data
DOI:10.5517/cc9qypm
from The Cambridge Structural Database
5 Related Records
5.1 Related Compounds with Annotation
Download
Medications (22)
Literature (61)
3D Structure (2)
fluticasone furoate
Bioactivities (124)
Patents (390)
medrysone
from PubChem
5.2 Related Compounds

Same Connectivity
46 records
Same Stereo
4 records
Same Isotope
36 records
Same Parent, Connectivity
55 records
Same Parent, Stereo
9 records
Same Parent, Isotope
45 records
Same Parent, Exact
6 records
Mixtures, Components, and

Neutralized Forms
31 records
Similar Compounds
2427 records
Similar Conformers
1485 records
from PubChem
5.3 Substances
5.3.1 Related Substances
All
130 records
Same
69 records
Mixture
61 records
from PubChem
5.3.2 Substances by Category

Download
Chemical Vendors (27)

Curation Efforts (1)
Governmental Organizations (5)
Journal Publishers (3)
NIH Initiatives (5)
Research and Development (28)
Subscription Services (5)
from PubChem
5.4 Entrez Crosslinks

PubMed
1205 records
Taxonomy
3 records
OMIM
1 record
Gene
39 records
from PubChem
6 Chemical Vendors
Refine/Analyze
Download
Vendor/Supplier
Purchasable Chemical
PubChem SID
DiscoveryGate
444036
10299475
ZINC
ZINC03920027
71824933
ChemScene
CS-1986
210279272
Berrchem
BR-72799
174476561
MedChemexpress MCE
HY-B0154
210281595
3062
251917852
80474-14-2
251916505
SAM001246583
46386601
SC-18196
251884139
SC-19333
251877001
RS0009
174561017
2100037
126592957
30107690
126621864
44005454
126653604
A&J Pharmtech CO., LTD.
AJ-47435
223556606
Chembase.cn
470
160963933
Syntree
ST2407016
249827492
AKos Consulting & Solutions
AKOS015895220
152034639
Hangzhou APIChem Technology
AC-457
92717930
ABI Chem
AC1L9FLD
104631189
FT-0082893
118048889
FT-0626494
164810442
Key Organics/BIONET
KS-1173
187072308
Boerchem
BC216013
196105643
Tocris Bioscience
2007
252156254
ABBLIS Chemicals
AB1010912
131465790
Ambinter
SBB071021
118318289
AvaChem Scientific
NIH Clinical Collection
labseeker
Wutech
ChemMol
Finetech Industry Limited
from PubChem
7 Drug and Medication Information

7.1 Drug Information
Drug Information: 1 of 7
Drug Name
Cutivate (from Drugs@FDA)
PubMed Health
Fluticasone
Drug Classes
Anti-Inflammatory, Corticosteroid, Intermediate, Corticosteroid, Strong (from

PubMed Health)
Drug Label
CUTIVATE (fluticasone propionate cream) Cream, 0.05% contains fluticasone

propionate [(6,11,16,17)-6,9,-difluoro-11-hydroxy-16-methyl-3-oxo-17-(1oxopropoxy)androsta-1,4-diene-17-carbothioic acid, S-fluoromethyl ester], a
synthetic fluorina...
Click here to see drug label(s) from DailyMed
Active Ingredient
Fluticasone propionate
Dosage Form
Lotion; Ointment
Route
Topical
Strength
0.05%; 0.005%
Market Status
Prescription
Company
Fougera Pharms
Patent
7300669 (from FDA Orange Book)

from FDA Drugs, DailyMed, and PubMed Health
Drug Name
Flonase (from Drugs@FDA)
Drug Label
Fluticasone propionate, the active component of FLONASE Nasal Spray, is a

synthetic corticosteroid having the chemical name S-(fluoromethyl)6,9difluoro-11-17-dihydroxy-16-methyl-3-oxoandrosta-1,4-diene-17-carbothioate,
17-propionate and the...
Active Ingredient
Dosage Form
Spray, metered
Route
Nasal
Strength
0.05mg/spray
Market Status
Prescription
Company
Glaxosmithkline
Drug Name
Flovent diskus 100 (from Drugs@FDA)
Active Ingredient
Dosage Form
Powder
Route
Inhalation
Strength
0.1mg/inh
Market Status
Prescription
Company
Glaxo Grp
Patent
5873360*PED; 5873360 (from FDA Orange Book)

Drug Name
Active Ingredient
Dosage Form
Powder
Route
Inhalation
Strength
0.25mg/inh
Market Status
Prescription
Company
Glaxo Grp
Patent

Drug Name
Active Ingredient
Dosage Form
Powder
Route
Inhalation
Strength
0.05mg/inh
Market Status
Prescription
Company
Glaxo Grp
Patent

Drug Name
Drug Label
Flovent hfa (from Drugs@FDA)

The active component of FLOVENT HFA 44 mcg Inhalation Aerosol, FLOVENT
HFA 110 mcg Inhalation Aerosol, and FLOVENT HFA 220 mcg Inhalation
Drug Label
Aerosol is fluticasone propionate, a corticosteroid having the chemical name
S-(fluoromethyl) 6,9-difluoro-11...
Active Ingredient
Dosage Form
Aerosol, metered
Route
Inhalation
Strength
0.22mg/inh; 0.11mg/inh; 0.044mg/inh
Market Status
Prescription
Company
Glaxo Grp
Patent
7500444*PED; 5674472; 6966467; 5658549*PED; 6170717*PED; 6997349;

6315173*PED; 7143908*PED; 6997349*PED; 6966467*PED; 6161724;
6435372*PED; 5674472*PED; 6431168*PED; 6510969; 7107986; 7143908;
6743413; 7832351; 6435372; 7500444; 6161724*PED; 6938796;
6938796*PED; 5658549; 6431168; 7832351*PED; 7107986*PED; 6596260;
7350676*PED; 6170717; 6315173; 6743413*PED; 7350676; 6510969*PED;
6596260*PED (from FDA Orange Book)
Drug Name
Fluticasone propionate (from Drugs@FDA)
Drug Label
Fluticasone propionate, the active component of Fluticasone Propionate

Nasal Spray USP, is a synthetic corticosteroid having the chemical name S(fluoromethyl)6,9-difluoro-11-17-dihydroxy-16-methyl-3-oxoandrosta-1,4diene-17-carbothioate, 17-...
Active Ingredient
Dosage Form
Ointment; Spray, metered; Cream; Lotion
Route
Nasal; Topical
Strength
0.05%; 0.005%; 0.05mg/spray
Market Status
Prescription
Company
Wockhardt; Apotex; Roxane; Glenmark Generics; Fougera Pharms; Hi Tech

Pharma; Perrigo New York; Tolmar; G And W Labs; Perrigo Israel
7.2 Therapeutic Uses

Androstadienes
National Library of Medicine's Medical Subject Headings online file (MeSH, 2009)
from HSDB
Fluticasone propionate nasal spray is indicated for the management of the nasal symptoms of seasonal and
perennial allergic and nonallergic rhinitis in adults and pediatric patients 4 years of age and older. /Included in US
product label/
US Natl Inst Health; DailyMed. Current Medication Information for Flonase (fluticasone propionate) spray (January 2008).
Available from, as of June 29, 2009: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=6415
from HSDB
Fluticasone propionate cream is a medium potency corticosteroid indicated for the relief of the inflammatory and
pruritic manifestations of corticosteroid-responsive dermatoses. Fluticasone propionate cream may be used with
caution in pediatric patients 3 months of age or older. The safety and efficacy of drug use for longer than 4 weeks
in this population have not been established. /Included in US product label/
US Natl Inst Health; DailyMed. Current Medication Information for Cutivate (fluticasone propionate) cream (April 2008).
from HSDB
Fluticasone propionate ointment is a medium potency corticosteroid indicated for the relief of the inflammatory
and pruritic manifestations of corticosteroid-responsive dermatoses in adult patients. /Included in US product
label/
US Natl Inst Health; DailyMed. Current Medication Information for Cutivate (fluticasone propionate) ointment (August 2007).
from HSDB
Fluticasone propionate inhalation powder is indicated for the maintenance treatment of asthma as prophylactic
therapy in adult and pediatric patients 4 years of age and older. It is also indicated for patients requiring oral
corticosteroid therapy for asthma. Many of these patients may be able to reduce or eliminate their requirement
for oral corticosteroids over time. /Included in US product label/
US Natl Inst Health; DailyMed. Current Medication Information for Flovent Diskus (fluticasone propionate) powder, metered
(November 2008). Available from, as of June 29, 2009: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=8742
from HSDB
Fluticasone propionate inhalation powder is NOT indicated for the relief of acute bronchospasm. /Included in US
product label/
from HSDB
7.3 Drug Warning

Intranasal fluticasone propionate generally is well tolerated. Adverse effects with intranasal fluticasone
propionate therapy usually are mild and local and resolve without specific treatment. The manufacturer states
that systemic corticosteroid effects were not reported with fluticasone nasal spray in controlled trials of up to 6
months' duration, but systemic effects (eg, growth suppression) have been reported with intranasal
corticosteroids, including fluticasone propionate, during postmarketing experience.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 2895
from HSDB
The most frequent adverse effects of fluticasone propionate nasal spray involve the nasal mucous membranes.
Epistaxis or sensations of nasal burning/irritation have been reported in 6-6.9 or 2.4-3.2%, respectively, of patients
receiving fluticasone propionate (100-200 ug once daily) in controlled studies. These adverse effects usually are
of short duration and rarely require changes in or discontinuance of therapy. Sensations of nasal burning may
result from excipients in the commercially available preparation since the frequency and severity of these effects
are similar in patients receiving an intranasal placebo vehicle with identical inactive ingredients. In addition, the
similar occurrence of adverse nasal effects in fluticasone propionate- or placebo-treated patients with seasonal
or perennial rhinitis may result from physical contact and irritation of the characteristically sensitive nasal
passages of these patients. Pharyngitis or cough has been reported in 6-7.8 or 3.6-3.8%, respectively, of patients
receiving the drug. Symptoms of asthma have occurred in 7.2 or 3.3% of those receiving 100 or 200 ug,
respectively, of fluticasone propionate once daily.

from HSDB
Other adverse nasopharyngeal or respiratory effects occurring in 1-3% of patients receiving fluticasone
propionate nasal spray include nasal secretions containing blood, nasal discharge, and bronchitis. Sneezing,
rhinorrhea, sinusitis, sore throat, throat irritation and dryness, hoarseness, voice changes, alteration or loss of
sense of taste and/or smell, nasal congestion or blockage, or nasal dryness has been reported in patients
receiving fluticasone propionate nasal spray in controlled studies or during postmarketing surveillance. Nasal
septum excoriation, ulceration, or nasal septum crusting also has been reported in patients receiving fluticasone
propionate nasal spray. It has been suggested that nasal septum crusting, nasal dryness accompanied by nasal
manipulation ("picking"), or nasal bleeding may predispose to the development of nasal perforation, which has
been reported rarely with intranasal administration of corticosteroids, including fluticasone propionate. In 2
patients who experienced nasal perforation with fluticasone propionate, both had previous septal surgery that
may have increased the risk of nasal perforation.
from HSDB
Localized candidal infections of the nose and/or pharynx have occurred rarely during fluticasone propionate
therapy. If a candidal infection is suspected, appropriate local anti-infective therapy and/or discontinuance of
intranasal corticosteroid therapy should be considered. Upper respiratory infection also has been reported with
intranasal fluticasone propionate therapy, but a causal relationship to the drug has not been established
from HSDB
Although not reported to date in patients receiving fluticasone propionate or other intranasal corticosteroids,
some clinicians caution that atrophic rhinitis potentially could develop during chronic therapy with an intranasal
corticosteroid, since atrophic dermatitis has occurred in patients treated with topical corticosteroids to the skin
for prolonged periods. However, the theoretical potential for nasal atrophy is thought to be less than that for
atrophic dermatitis because of the smaller residence time of the intranasal corticosteroid on the nasal mucosa
compared with that of topical corticosteroids on the skin. Rhinoscopic assessment or nasal examination of
patients with rhinitis treated continuously with intranasal fluticasone propionate for 6-12 months has shown no
evidence of serious mucosal damage.
from HSDB
Adrenal suppression, based on mean plasma cortisol, morning plasma cortisol, or urinary 17-ketogenic steroid
(17-KS) determinations, has not been observed to date when fluticasone propionate was administered
intranasally in adults receiving 200 ug daily for up to 12 months or in children (aged 4-11 years) receiving
intranasal fluticasone spray 100-200 ug daily for 2-4 weeks. In addition, no evidence of growth suppression was
noted in a 1-year, placebo-controlled study in children 3-9 years of age receiving fluticasone propionate 200 ug
once daily... While no clinically important alterations in plasma cortisol were observed in patients with asthma
receiving orally inhaled fluticasone propionate dosages of 200-1500 ug daily for up to 1 year, a relationship
between plasma fluticasone propionate concentrations and inhibitory effects on stimulated cortisol production
has been demonstrated after 4 weeks of treatment with fluticasone propionate inhalation aerosol. ...The
manufacturer states that although systemic effects have been minimal with recommended doses of fluticasone
propionate nasal spray, the potential risk of such effects increases with larger doses; therefore, larger-thanrecommended doses of fluticasone propionate nasal spray should be avoided. The effect of intranasal
fluticasone propionate on the HPA-axis response to stress (eg, surgery) is not known. Intranasal administration of
usual dosages of fluticasone propionate apparently produces less HPA-axis suppression than intranasal
administration of usual dosages of dexamethasone phosphate; however, comparative studies have not been
conducted to date.
from HSDB
Headache has been reported in 6.6-16.1% of patients receiving intranasal fluticasone propionate therapy.
Menstrual cramps also have been reported in patients receiving the drug, although a causal relationship has not
been established. Nausea and vomiting have been reported in 2.6-4.8% of adults and children receiving
fluticasone in controlled clinical trials. Dizziness, abdominal pain, diarrhea, fever, flu-like symptoms, or aches and
pains have been reported in 1-3% of adults and children receiving fluticasone in controlled clinical trials.
Drowsiness/lethargy/fatigue or arthralgia has occurred infrequently in patients receiving intranasal fluticasone
propionate. Immediate hypersensitivity reactions (eg, wheezing, contact dermatitis, rash, dyspnea,
anaphylaxis/anaphylactoid reactions, pruritus, urticaria, angioedema, edema of the face and tongue,
bronchospasm) have been reported during postmarketing surveillance or in controlled clinical trials with
intranasal administration of fluticasone propionate.
from HSDB
Cataracts, ocular dryness and irritation, conjunctivitis, blurred vision, glaucoma, and increased intraocular
pressure have been reported with intranasal administration of corticosteroids, including fluticasone. In a
controlled, comparative study, ophthalmologic abnormalities (eg, retinal changes, lenticular opacities) were noted
after 12 and 24 weeks of therapy in a similar percentage of patients receiving intranasal fluticasone propionate,
beclomethasone, or placebo; however, none of the ocular changes were of the type attributed to systemic effects
of corticosteroid therapy (eg, posterior subcapsular cataracts, increased intraocular pressure).
from HSDB
Although systemic effects have been minimal with recommended dosages of fluticasone propionate nasal spray,
potential risk increases with higher dosages. Therefore, higher than recommended dosages of fluticasone
propionate nasal spray should be avoided since hypercorticism and suppression of HPA function may occur. If
such systemic effects occur, the dosage of fluticasone propionate nasal spray should be reduced slowly and the
drug discontinued in accordance with accepted procedures for discontinuing oral corticosteroid therapy
from HSDB
Fluticasone propionate nasal spray should be used with caution in patients receiving systemic corticosteroids in
an alternate-day or daily dosing regimen for any disease, since concomitant use of the drugs could increase the
likelihood of HPA-axis suppression compared with therapeutic dosages of either drug alone. In addition,
concomitant use of fluticasone propionate nasal spray with other inhaled corticosteroids could increase the risk
of manifestations of hypercorticism and/or suppression of HPA function.
from HSDB
Patients who have received systemic corticosteroids for prolonged periods and are being switched to treatment
with topical corticosteroids (eg, fluticasone propionate nasal spray) should be monitored carefully since
corticosteroid withdrawal symptoms (eg, joint pain, muscular pain, lassitude, depression), acute adrenal
insufficiency, or severe symptomatic exacerbation of asthma or other clinical conditions may occur.
from HSDB
Although manifestations of Cushing's syndrome (eg, hypertension, glucose intolerance, cushingoid features)
have not been associated with intranasal fluticasone propionate therapy to date, the possibility of their
occurrence should be considered in patients who are particularly sensitive to corticosteroid effects or when usual
dosages of the drug are exceeded.
from HSDB
Patients should be advised that intranasal fluticasone propionate should be used at regular intervals to be
therapeutically effective. In addition, patients generally should be advised that the full benefits of the drug may
not be achieved for several days and that use of topical nasal decongestants or oral antihistamines may be
necessary until the effects of intranasal fluticasone propionate therapy are fully manifested. Patients also should
be advised not to exceed the prescribed dosage. Patients with severe allergies should be instructed to avoid
exposure to allergens during intranasal fluticasone propionate therapy to prevent the occurrence of severe
allergic symptoms in the eyes and/or lower respiratory tract. Patients should be instructed to contact their
physician during intranasal fluticasone propionate therapy if signs or symptoms of the condition do not improve,
if the condition worsens, or if sneezing or nasal irritation occurs.
from HSDB
Glucocorticoids, especially in large doses, increase susceptibility to and mask symptoms of infection. Because of
the inhibitory effect of these drugs on wound healing, patients with recent nasal septal ulcers, nasal surgery, or
nasal trauma should not use intranasal corticosteroids until healing has occurred.
from HSDB
Patients who are taking immunosuppressant drugs while receiving corticosteroids have increased susceptibility
to infections compared with healthy individuals, and certain infections (eg, varicella [chickenpox], measles) can
have a more serious or even fatal outcome in such patients, particularly in children. In patients who have not had
these diseases, particular care should be taken to avoid exposure. The relationship of dose, route of
administration, and duration of corticosteroid therapy to the risk of developing a disseminated infection is not
known, nor is the contribution of the underlying disease and/or prior corticosteroid therapy. Patients receiving
corticosteroids who are potentially immunosuppressed should be warned of the risk of exposure to certain
infections (eg, chickenpox, measles) and of the importance of obtaining medical advice if such exposure occurs.
If exposure to varicella or measles occurs in such individuals, administration of varicella zoster immune globulin
(VZIG) or immune globulin, respectively, may be indicated. If varicella develops, treatment with an antiviral agent
(eg, acyclovir) may be considered.
from HSDB
Fluticasone propionate nasal spray is contraindicated in patients with known hypersensitivity to the drug or other
ingredients in the formulation (the formulation does not contain fluorocarbons).
from HSDB
Use of excessive dosages of corticosteroids may lead to manifestations of hypercorticism, suppression of HPA
function, and/or suppression of growth in children or adolescents. Inhibitory effects on short-term growth rate (as
determined by knemometry studies of lower leg growth) have been observed in asthmatic children and
adolescents receiving orally inhaled corticosteroids (eg, beclomethasone dipropionate, fluticasone propionate).
However, the relationship between short-term changes in lower leg growth and long-term effects on growth
currently are unclear. ... Clinicians should monitor closely (eg, via stadiometry) the growth of children and
adolescents taking corticosteroids by any route of administration; if growth rate is affected, the clinician should
weigh the potential benefits of corticosteroid therapy against the possibility of growth suppression.
from HSDB
Fluticasone propionate should be used with caution in nursing women, since it is not known whether the drug is
distributed into milk in humans.
from HSDB
FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are
lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if
the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./
from HSDB
During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving
fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and
adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended
unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
from HSDB
Intranasal corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous
infections of the respiratory tract; untreated local or systemic fungal or bacterial infections; systemic viral or
parasitic infections; or ocular herpes simplex.
from HSDB
In clinical studies with fluticasone propionate administered intranasally, the development of localized infections
of the nose and pharynx with Candida albicans has occurred only rarely. When such an infection develops, it may
require treatment with appropriate local therapy and discontinuation of treatment with Fluticasone propionate
nasal spray. Patients using Fluticasone propionate nasal spray over several months or longer should be
examined periodically for evidence of Candida infection or other signs of adverse effects on the nasal mucosa.
from HSDB
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses /of topical fluticasone
propionate/ due to their larger skin surface to body mass ratios.
from HSDB
Fluticasone propionate cream contains the excipient imidurea which releases traces of formaldehyde as a
breakdown product. Formaldehyde may cause allergic sensitization or irritation upon contact with the skin.
from HSDB
If irritation develops, Fluticasone propionate cream should be discontinued and appropriate therapy instituted.
Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than
noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation
should be corroborated with appropriate diagnostic patch testing.
from HSDB
Parents of pediatric patients should be advised not to use this medication in the treatment of diaper dermatitis.
Fluticasone propionate cream should not be applied in the diaper areas as diapers or plastic pants may
constitute occlusive dressing.
from HSDB
Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with
endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical
administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities
in human milk.
from HSDB
This medication should not be used on the face, underarms, or groin areas unless directed by a physician.
from HSDB
HPA axis suppression, Cushing syndrome, linear growth retardation, delayed weight gain, and intracranial
hypertension have been reported in pediatric patients receiving topical corticosteroids. ... Manifestations of
intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.
from HSDB
The total incidence of adverse reactions associated with the use of Fluticasone propionate cream was
approximately 4%. These adverse reactions were usually mild; self-limiting; and consisted primarily of pruritus,
dryness, numbness of fingers, and burning. These events occurred in 2.9%, 1.2%, 1.0%, and 0.6% of patients,
respectively.
from HSDB
The following local adverse reactions have been reported infrequently with topical corticosteroids, and they may
occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions
are listed in an approximately decreasing order of occurrence: irritation, folliculitis, acneiform eruptions,
hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, and
miliaria. Also, there are reports of the development of pustular psoriasis from chronic plaque psoriasis following
reduction or discontinuation of potent topical corticosteroid products.
from HSDB
Fluticasone propionate inhalation powder is contraindicated in the primary treatment of status asthmaticus or
other acute episodes of asthma where intensive measures are required.
from HSDB
Particular care is needed for patients who are transferred from systemically active corticosteroids to fluticasone
propionate inhalation powder because deaths due to adrenal insufficiency have occurred in patients with asthma
during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.
After withdrawal from systemic corticosteroids, a number of months are required for recovery of HPA function.
from HSDB
Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be
most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn.
During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when
exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe
electrolyte loss. Although fluticasone propionate inhalation powder may provide control of asthma symptoms
during these episodes, in recommended doses it supplies less than normal physiological amounts of
corticosteroid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with
these emergencies.
from HSDB
During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic
corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact
their physicians for further instruction. These patients should also be instructed to carry a warning card
indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe
asthma attack.
from HSDB
Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after
transferring to fluticasone propionate inhalation powder. ...Lung function (FEV1 or AM PEF), beta-agonist use,
and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition to
monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal
insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension.
from HSDB
Transfer of patients from systemic corticosteroid therapy to fluticasone propionate inhalation powder may
unmask conditions previously suppressed by the systemic corticosteroid therapy, eg, rhinitis, conjunctivitis,
eczema, arthritis, and eosinophilic conditions.
from HSDB
Fluticasone propionate inhalation powder is not to be regarded as a bronchodilator and is not indicated for rapid
relief of bronchospasm.
from HSDB
As with other inhaled medications, bronchospasm may occur with an immediate increase in wheezing after
dosing. If bronchospasm occurs following dosing with fluticasone propionate inhalation powder, it should be
treated immediately with a fast-acting inhaled bronchodilator. Treatment with fluticasone propionate inhalation
powder should be discontinued and alternative therapy instituted.
from HSDB
Patients should be instructed to contact their physicians immediately when episodes of asthma that are not
responsive to bronchodilators occur during the course of treatment with fluticasone propionate inhalation
powder. During such episodes, patients may require therapy with oral corticosteroids.
from HSDB
In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions, with
some patients presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome /(allergic
eosinophilic vasculitis)/, a condition that is often treated with systemic corticosteroid therapy. These events
usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy
following the introduction of fluticasone propionate. Cases of serious eosinophilic conditions have also been
reported with other inhaled corticosteroids in this clinical setting. Physicians should be alert to eosinophilia,
vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their
patients. A causal relationship between fluticasone propionate and these underlying conditions has not been
established.
from HSDB
7.4 Drug Indication

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 maintenance treatment of asthma as prophylactic therapy and for patients requiring
oral corticosteroid therapy for asthma.
from DrugBank
8 Pharmacology and Biochemistry

8.1 Pharmacology
Fluticasone is an extremely potent vasoconstrictor and anti-inflammatory agent. Its effectiveness in inhaled
forms is due to its direct local effect.
from DrugBank
Fluticasone Propionate is the propionate salt form of fluticasone, a synthetic trifluorinated glucocorticoid
receptor agonist with antiallergic, antiinflammatory and antipruritic effects. Binding and activation of the
glucocorticoid receptor results in the activation of lipocortin that in turn inhibits cytosolic phospholipase A2,
which triggers cascade of reactions involved in synthesis of inflammatory mediators, such as prostaglandins and
leukotrienes. Secondly, mitogen-activated protein kinase (MAPK) phosphatase 1 is induced, thereby leads to
dephosphorylation and inactivation of Jun N-terminal kinase directly inhibiting c-Jun mediated transcription.
Finally, transcriptional activity of nuclear factor (NF)-kappa-B is blocked, thereby inhibits the transcription of
cyclooxygenase 2, which is essential for prostaglandin production.
from NCIt
8.2 MeSH Pharmacological Classification

Dermatologic Agents
Drugs used to treat or prevent skin disorders or for the routine care of skin. See a list of PubChem compounds
matching this category.
from MeSH
Anti-Inflammatory Agents
Substances that reduce or suppress INFLAMMATION. See a list of PubChem compounds matching this
category.
from MeSH
Bronchodilator Agents
Agents that cause an increase in the expansion of a bronchus or bronchial tubes. See a list of PubChem
compounds matching this category.
from MeSH
Anti-Allergic Agents
Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory
mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations
Annual, 1994, p475) See a list of PubChem compounds matching this category.
from MeSH
8.3 Absorption, Distribution and Excretion

Fluticasone propionate is poorly absorbed from the respiratory and GI tracts following nasal inhalation of the
drug as an aqueous spray. Based on indirect calculations, intranasal fluticasone propionate has an absolute
systemic bioavailability of less than 2%. A major portion of an intranasal dose of corticosteroids is swallowed and
undergoes extensive first-pass metabolism in the liver. In patients with allergic rhinitis receiving intranasal
fluticasone propionate for 2-3 weeks, plasma concentrations were above the level of detection of the assay (50
pg/mL) only when recommended dosages were exceeded, and in those instances, only in occasional samples at
low concentrations.
from HSDB
Limited data from studies in which radiolabeled fluticasone propionate has been administered orally indicate that
the drug is poorly absorbed from the GI tract and undergoes rapid first-pass metabolism in the liver. Preliminary
data from a dose-ranging study suggests that the amount of unchanged fluticasone propionate in plasma
increases with dose following oral administration, but the bioavailability of the radiolabeled drug averaged about
1% or less after oral doses of 1-40 mg.
from HSDB
Following oral administration of 1 or 16 mg of radiolabeled propionylfluticasone in a few healthy individuals, peak
plasma radioactivity levels (expressed as fluticasone propionate equivalents) averaging approximately 1.3 or 9.1
ng/mL, respectively, were achieved within 0.5-6 hours. Since no unchanged fluticasone propionate was detected
in plasma for up to 6 hours after oral administration of unlabeled fluticasone propionate given on a separate
occasion, the plasma radioactivity noted after administration of the radiolabeled drug was presumed to be
fluticasone propionate metabolites. It has been suggested that the presence of small amounts (50-170 pg/mL) of
fluticasone propionate in plasma from 6-24 hours after the dose in these individuals potentially may represent
rectal reabsorption of unmetabolized drug.
from HSDB
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the
vehicle and the integrity of the epidermal barrier. Occlusive dressing enhances penetration. Topical
corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the
skin increase percutaneous absorption.
from HSDB
In a human study of 12 healthy males receiving 12.5 g of 0.05% fluticasone propionate cream twice daily for 3
weeks, plasma levels were generally below the level of quantification (0.05 ng/mL). In another study of 6 healthy
males administered 25 g of 0.05% fluticasone propionate cream under occlusion for 5 days, plasma levels of
fluticasone ranged from 0.07 to 0.39 ng/mL.
from HSDB
In an animal study using radiolabeled 0.05% fluticasone propionate cream and ointment preparations, rats
received a topical dose of 1 g/kg for a 24-hour period. Total recovery of radioactivity was approximately 80% at
the end of 7 days. The majority of the dose (73%) was recovered from the surface of the application site. Less
than 1% of the dose was recovered in the skin at the application site. Approximately 5% of the dose was absorbed
systemically through the skin. Absorption from the skin continued for the duration of the study (7 days),
indicating a long retention time at the application site.
from HSDB
...The majority of the fluticasone propionate delivered to the lung is systemically absorbed. The systemic
bioavailability of fluticasone propionate from the Diskus device in healthy volunteers averages 18%.
from HSDB
Systemic exposure as measured by AUC in healthy subjects (N = 24) who received 8 inhalations, as a single dose,
of fluticasone propionate HFA using the 44-, 110-, and 220-ug strengths increased proportionally with dose. The
geometric means (95% CI) of AUC0-24 hr for the 44-, 110-, and 220-ug strengths were 488 (362, 657); 1,284 (904;
1,822); and 2,495 (1,945; 3,200) pg.hr/mL, respectively, and the geometric means of Cmax were 126 (108, 148),
254 (202, 319), and 421 (338, 524) pg/mL, respectively. Systemic exposure from fluticasone propionate HFA 220
ug was 30% lower than that from the fluticasone propionate CFC inhaler. Systemic exposure was measured in
patients with asthma who received 2 inhalations of fluticasone propionate HFA 44 ug (n = 20), 110 ug (n = 15), or
220 ug (n = 17) twice daily for at least 4 weeks. The geometric means (95% CI) of AUC0-12 hr for the 44-, 110-,
and 220-ug strengths were 76 (33, 175), 298 (191, 464), and 601 (431, 838) pg.hr/mL, respectively. Cmax occurred
in about 1 hour, and the geometric means were 25 (18, 36), 61 (46, 81), and 103 (73, 145) pg/mL, respectively.
US Natl Inst Health; DailyMed. Current Medication Information for Flovent-HFA (fluticasone propionate) aerosol, metered (July
2008). Available from, as of June 29, 2009: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=7947
from HSDB
Peak steady-state fluticasone propionate plasma concentrations in adult patients with asthma (N = 11) ranged
from undetectable to 266 pg/mL after a 500-mcg twice-daily dosage of fluticasone propionate inhalation powder
using the Diskus device. The mean fluticasone propionate plasma concentration was 110 pg/mL.
from HSDB
Although fluticasone propionate is widely distributed into most tissues following iv administration, distribution of
the drug following intranasal administration has not been described. Following iv administration, the volume of
distribution for fluticasone propionate is 4.2 L/kg. Fluticasone propionate is approximately 91% bound to human
plasma proteins; protein binding demonstrates no obvious relationship to drug concentration. Fluticasone
propionate is weakly and reversibly bound to erythrocytes and equilibrates freely between erythrocytes and
plasma. Fluticasone propionate is not appreciably bound to human transcortin (corticosteroid-binding globulin).
from HSDB
Fluticasone propionate crosses the placenta in rats or rabbits following oral administration of fluticasone
propionate 100 or 300 ug/kg, respectively (approximately 4 or 25 times, respectively, the maximum daily
intranasal dosage in adults on a ug/sq m basis). It is not known if fluticasone propionate is distributed into
human milk following intranasal administration; however, other corticosteroids are distributed into human milk.
from HSDB
In lactating rats, subcutaneous administration of tritiated fluticasone propionate (10 ug/kg, approximately onethird the maximum recommended daily intranasal dosage in adults on a ug/sq m basis) resulted in measurable
radioactivity in both plasma and milk.
from HSDB
Plasma clearance of the drug ranges from 623-998 mL/minute; total blood clearance (plasma clearance adjusted
for packed cell volume) of iv fluticasone propionate averages 1093 mL/minute and approximates that of liver
blood flow, with renal clearance accounting for less than 0.02% of total body clearance.
from HSDB
Following oral administration of radiolabeled drug, less than 5% of the dose was excreted in urine. ...Total fecal
excretion of fluticasone propionate has been reported to range from 87-100% of the oral dose. In 2 healthy men
receiving oral fluticasone propionate, fecal recovery of unchanged drug was 9 and 20% after a 1-mg dose and 54
and 75% after a 16-mg dose. The increase in fecal excretion of unchanged fluticasone propionate with increased
dose has been attributed to insolubility of the drug rather than to biliary elimination. ... When a single oral 5-mg
dose of fluticasone propionate was administered to patients with an ileostomy, 73% of the dose was recovered in
the ileostomy effluent within 12 hours.
from HSDB
The 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.
from DrugBank
Route of Elimination
Less 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.
from DrugBank
Volume of Distribution
IV administration = 4.2 L/kg
from DrugBank
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.
from DrugBank
8.4 Metabolism/Metabolites
Fluticasone propionate is rapidly metabolized in the liver by the cytochrome P-450 isoenzyme CYP3A4; the
principal metabolite is the inactive 17beta-carboxylic acid derivative. ... Of the total radioactivity recovered in
urine, 18% represented the inactive 17beta-carboxylic acid derivative of fluticasone propionate, 12% represented a
less polar metabolite, and the remainder represented more polar metabolites. ... The 17beta-carboxylic acid
metabolite of fluticasone propionate accounted for 3-40% of fecal excretion.
from HSDB
The inactive /17beta-carboxylic acid derivative/ had less affinity (approximately 1/2,000) than the parent drug for
the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal
studies. Other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man.
from HSDB
No metabolites of fluticasone propionate were detected in an in vitro study of radiolabeled fluticasone propionate
incubated in a human skin homogenate.
from HSDB
Fluticasone propionate is metabolized in the liver by cytochrome P450 3A4-mediated hydrolysis of the 5fluoromethyl 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.
from DrugBank
8.5 Biological Half-Life

Following intravenous dose of 1 mg in healthy volunteers, fluticasone propionate showed polyexponential
kinetics and had an average terminal half-life of 7.2 hours (range, 3.2 to 11.2 hours).
from HSDB
The apparent elimination half-life of fluticasone propionate after iv administration is approximately 3 hours.
from HSDB
Terminal elimination half-life = 7.8 hours
from DrugBank
8.6 Mechanism of Action

Fluticasone propionate is a highly selective agonist at the human glucocorticoid receptor with negligible activity
at androgen, estrogen, or mineralocorticoid receptors. In preclinical studies, fluticasone propionate reportedly
exhibited weak progesterone-like activity. However, as plasma concentrations of fluticasone propionate are very
low following intranasal administration of the drug in recommended doses, the clinical importance of this finding
is not known. The therapeutic effects of fluticasone propionate are thought to result from local actions of the
deposited inhaled dose on the nasal mucosa rather than from the systemic actions of the swallowed portion of
the dose.
from HSDB
The exact mechanism(s) of anti-inflammatory action of corticosteroids in allergic rhinitis remains unknown, but
may involve reductions in the following: number of mediator cells (basophils, eosinophils, helper-inducer [CD4+,
T4] T-cells, mast cells, and neutrophils) in the nasal mucosa, nasal reactivity to allergens, and release of
inflammatory mediators and proteolytic enzymes. Following exposure of patients with a history of allergic rhinitis
to allergen, eosinophils, basophils, mast cells, T cells, and neutrophils appear to infiltrate nasal secretions and
mucosa, releasing inflammatory mediators that generate allergic responses such as pruritus, sneezing,
rhinorrhea, and nasal edema. /Corticosteroids/
from HSDB
Other mechanisms by which corticosteroids may improve symptoms of allergic rhinitis may involve inhibition of
postcapillary venule dilation and permeability and facilitation of nasomucociliary clearance of nasal secretions.
Patients receiving short- and long-term treatment with intranasal fluticasone propionate have demonstrated
decreases in nasal turbinate swelling and mucosal inflammation. As inflammatory changes occur during periods
of increased nasal hyperresponsiveness, the degree of response to nasal secretory stimuli has been used as an
indirect measure of inflammation. In patients with asymptomatic seasonal allergic rhinitis, pretreatment with
intranasal fluticasone propionate for 2-6 weeks prior to challenge with allergens or inflammatory
mediatorsgenerally reduced the release of tryptase, histamine, eosinophilic cationic protein, and prostaglandin D2
in nasal biopsies or nasal lavage fluid; concentrations of eosinophils or activated eosinophils, CD4+ T-cells, and
basophils also were reduced. /Corticosteroids/
from HSDB
Like other topical corticosteroids, fluticasone propionate has anti-inflammatory, antipruritic, and vasoconstrictive
properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear.
However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively
called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of
inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor,
arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
from HSDB
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 antiinflammatory 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.
from DrugBank
9 Use and Manufacturing

9.1 Impurities
6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-3-oxo-17-propanoyloxy)androsta-1,4-diene-17beta-carboxylic
acid
Council of Europe, European Directorate for the Quality of Medicines. European Pharmacopoeia, 5th Ed., Volume 2; Strasbourg,
France, p.1628 (2004)
from HSDB
[(6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-3-oxo-17-(propanoyloxy)androsta-1,4-dien-17betayl]carbonyl]sulphenic acid
France, p.1628 (2004)
from HSDB
6alpha,9-difluoro-17-[[(fluoromethyl)sulpanyl]carbonyl]-11beta-hydroxy-16alpha-methyl-3-oxoandrosta-1,4-dien17alpha-yl acetate
France, p.1628 (2004)
from HSDB
6alpha,9-difluoro-17-[(methylsulphanyl)carbonyl]-11beta-hydroxy-16alpha-methyl-3-oxoandrosta-1,4-dien17alpha-yl propanoate
France, p.1628 (2004)
from HSDB
6alpha,9difluoro-17[[(fluoromethyl)sulphanyl]carbonyl]-16alpha-methyl-2,11-dioxoandrosta-1,4-dien-17alpha-yl
propanoate
France, p.1628 (2004)
from HSDB
6alpha,9difluoro-17-[[(fluoromethyl)sulphanyl]carbonyl]-11beta-hydroxy-16alpha-methyl-3-oxoandrost-4-en17alpha-yl propanoate
France, p.1628 (2004)
from HSDB
6alpha,9-difluoro-17-[[(fluoromethyl)sulphanyl]carbonyl]-11beta-hydroxy-16alpha-methyl-3-oxoandrosta-1,4-dien17alpha-yl 6alpha,9-difluoro-11beta,17-dihydroxy-16alpha-methyl-3-oxoandrosta-1,4-diene-17beta-carboxylate
France, p.1628 (2004)
from HSDB
17,17'-(disulphanediyldicarbonyl)bis(6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-3-oxoandrosta-1,4-dien17alpha-yl) dipropanoate
France, p.1628 (2004)
from HSDB
17,17'-(trisulphanediyldicarbonyl)bis(6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-3-oxoandrosta-1,4-dien17alpha-yl) dipropanoate
France, p.1628 (2004)
from HSDB
9.2 Formulations/Preparations
Fluticasone propionate nasal spray is an aqueous suspension of microfine fluticasone propionate for topical
administration to the nasal mucosa by means of a metering, atomizing spray pump. Fluticasone propionate nasal
spray also contains microcrystalline cellulose and carboxymethylcellulose sodium, dextrose, 0.02% w/w
benzalkonium chloride, polysorbate 80, and 0.25% w/w phenylethyl alcohol, and has a pH between 5 and 7.
/Fluticasone propionate/
from HSDB
Each gram of fluticasone propionate cream contains fluticasone propionate 0.5 mg in a base of propylene glycol,
mineral oil, cetostearyl alcohol, Ceteth-20, isopropyl myristate, dibasic sodium phosphate, citric acid, purified
water, and imidurea as preservative. /Fluticasone propionate/
from HSDB
Each gram of fluticasone propionate ointment contains fluticasone propionate 0.05 mg in a base of liquid
paraffin, microcrystalline wax, propylene glycol, and sorbitan sesquioleate. /Fluticasone propionate/
US Natl Inst Health; DailyMed. Current Medication Information for Cutivate (fluticasone propionate) ointment (August 2007).
from HSDB
Fluticasone propionate Diskus is a specially designed plastic inhalation delivery system containing a double-foil
blister strip of a powder formulation of fluticasone propionate intended for oral inhalation only. The Diskus
inhalation unit, which is the delivery component, is an integral part of the drug product. Each blister on the doublefoil strip within the unit contains 50 mcg of microfine fluticasone propionate in 12.5 mg of formulation containing
lactose (which contains milk proteins). /Fluticasone propionate/
from HSDB
Fluticasone propionate HFA inhalation aerosols (44, 110, 220 ug) are pressurized metered-dose aerosol units
fitted with a counter. ... Each unit contains a microcrystalline suspension of fluticasone propionate (micronized)
in propellant HFA-134a (1,1,1,2-tetrafluoroethane). It contains no other excipients. /Fluticasone propionate/
from HSDB
10 Identification
10.1 Analytic Laboratory Methods
Analyte: fluticasone propionate; matrix: chemical identification; procedure: infrared absorption
spectrophotometry with comparison to standards /Fluticasone propionate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 31/The National Formulary, NF 26; Rockville, MD: U.S.
Pharmacopeial Convention, Inc., p.2218 (2008)
from HSDB
Analyte: fluticasone propionate; matrix: chemical identification; procedure: retention time of the major peak of the
liquid chromatogram with comparison to standards /Fluticasone propionate/
from HSDB
Analyte: fluticasone propionate; matrix: chemical purity; procedure: liquid chromatography with ultraviolet
detection at 239 nm and comparison to standards /Fluticasone propionate/
from HSDB
Analyte: fluticasone propionate; matrix: pharmaceutical preparation (nasal spray); procedure: infrared absorption
spectrophotometry with comparison to standards (chemical identification) /Fluticasone propionate/
from HSDB
Analyte: fluticasone propionate; matrix: pharmaceutical preparation (nasal spray); procedure: retention time of
the major peak of the liquid chromatogram with comparison to standards (chemical identification) /Fluticasone
propionate/
from HSDB
Analyte: fluticasone propionate; matrix: pharmaceutical preparation (nasal spray); procedure: liquid
chromatography with ultraviolet detection between 210 and 239 nm and comparison to standards (chemical
purity) /Fluticasone propionate/
from HSDB
Analyte: fluticasone propionate; matrix: chemical identification; procedure: infrared absorption
spectrophotometry with comparison to standards /Fluticasone propionate/
France, p.1627 (2004)
from HSDB
Analyte: fluticasone propionate; matrix: chemical identification; procedure: retention time of the major peak of the
liquid chromatogram with comparison to standards /Fluticasone propionate/
France, p.1627 (2004)
from HSDB
Analyte: fluticasone propionate; matrix: chemical purity; procedure: liquid chromatography with ultraviolet
detection at 239 nm and comparison to standards /Fluticasone propionate/
France, p.1627 (2004)
from HSDB
10.2 Clinical Laboratory Methods

Analyte: fluticasone propionate; matrix: pharmaceutical preparation (body wash, cream, gel, lotion, shampoo,
spray); procedure: high-performance liquid chromatography with ultraviolet detection at 240 nm; limit of
detection: 0.001% /Fluticasone propionate/
Reepmeyer JC; J Liq Chromotogr Rel Technol 24: 693-709 (2001). As cited in: Lunn G; HPLC Methods for Recently Approved
Pharmaceuticals. New York, NY: John Wiley & Sons, p.272 (2005)
from HSDB
Analyte: fluticasone propionate; matrix: pharmaceutical preparation; procedure: high-performance liquid
chromatography with ultraviolet detection at 214 nm /Fluticasone propionate/
Frame LA et al; J Chromatogr A 798: 243-9 (1998). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CDROM. New York, NY: John Wiley & Sons (2000)
from HSDB
Analyte: fluticasone propionate; matrix: blood (plasma); procedure: high-performance liquid chromatography with
mass spectrometry detection; limit of quantitation: 20 pg/mL /Fluticasone propionate/
Callejas SL et al; J Chromatogr B 718: 243-250 (1998). As cited in: Lunn G; HPLC Methods for Recently Approved
Pharmaceuticals. New York, NY: John Wiley & Sons, p.270 (2005)
from HSDB
11 Safety and Hazards

11.1 Accidental Release Measures
11.1.1 Disposal Methods
SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to
significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with
environmental regulatory agencies for guidance on acceptable disposal practices.
from HSDB
11.2 Handling and Storage

11.2.1 Storage Conditions
Fluticasone propionate HFA contents /are/ under pressure: Do not puncture. Do not use or store near heat or
open flame. Exposure to temperatures above 120 deg F may cause bursting. Never throw into fire or incinerator.
Store at 25 deg C (77 deg F); excursions permitted to 15-30 deg C (59-86 deg F). Store the inhaler with the
mouthpiece down. For best results, the inhaler should be at room temperature before use.
from HSDB
Store /fluticasone propionate inhalation powder/ at controlled room temperature, 20 to 25 deg C (68 to 77 deg F)
in a dry place away from direct heat or sunlight. Keep out of reach of children. The Diskus inhalation device is not
reusable. The device should be discarded 6 weeks after removal from the moisture-protective foil pouch or after
all blisters have been used (when the dose indicator reads "0"), whichever comes first. Do not attempt to take the
device apart.
from HSDB
Fluticasone propionate cream /and ointment should be/ stored between 2 and 30 deg C (36 and 86 deg F).
from HSDB
Fluticasone propionate nasal pump spray should be stored at 4-30 deg C.
from HSDB
11.3 Regulatory Information

11.3.1 FDA Requirements
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed
prescription drug products, incl fluticasone propionate, approved on the basis of safety and effectiveness by FDA
under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Fluticasone propionate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of
July 9, 2009: http://www.accessdata.fda.gov/scripts/cder/ob/docs/queryai.cfm
from HSDB
12 Toxicity
12.1 Toxicological Information
12.1.1 Interactions
A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4
inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced
serum cortisol concentrations.
from HSDB
In a placebo-controlled crossover study in 8 healthy volunteers, coadministration of a single dose of orally inhaled
fluticasone propionate with multiple doses of ketoconazole to steady state resulted in increased plasma
fluticasone propionate exposure, a reduction in plasma cortisol AUC, and no effect on urinary excretion of
cortisol. Caution should be exercised when fluticasone propionate is coadministered with ketoconazole and other
known potent cytochrome P450 3A4 inhibitors.
from HSDB
12.1.2 Antidote and Emergency Treatment

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not
breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or
pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing
water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down
position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal
body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier
Mosby, St. Louis, MO 2005, p. 160
from HSDB
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if
necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by
nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock
and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes
immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use
emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can
swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after
decontamination ... . /Poisons A and B/
Mosby, St. Louis, MO 2005, p. 160
from HSDB
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who
is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation
techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... .
Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm
and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/.
Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of
hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or
lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Mosby, St. Louis, MO 2005, p. 160-1
from HSDB
12.1.3 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ Repeat oral doses up to 80 mg daily for 10 days in volunteers and repeat oral
doses up to 10 mg daily for 14 days in patients were well tolerated. Adverse reactions were of mild or moderate
severity, and incidences were similar in active and placebo treatment groups.
from HSDB
/HUMAN EXPOSURE STUDIES/ Intranasal administration of 2 mg of fluticasone propionate twice daily for 7 days
to healthy human volunteers was well tolerated. Single oral doses up to 16 mg have been studied in human
volunteers with no acute toxic effects reported.
from HSDB
/SIGNS AND SYMPTOMS/ Particular care is needed for patients who are transferred from systemically active
corticosteroids to fluticasone propionate inhalation powder because deaths due to adrenal insufficiency have
occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically
available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are
required for recovery of HPA function.
from HSDB
/SIGNS AND SYMPTOMS/ Chronic overdosage may result in signs/symptoms of hypercorticism.
from HSDB
12.1.4 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ No evidence of carcinogenicity was seen in mice
receiving oral fluticasone propionate dosages up to 1 mg/kg (approximately 20 times the maximum
recommended daily intranasal dosage in adults and approximately 10 times the maximum recommended daily
intranasal dosage in children on a ug/sq m basis) for 78 weeks or in rats receiving inhaled fluticasone propionate
dosages up to 57 ug/kg (approximately 2 times the maximum recommended daily intranasal dosage in adults
and approximately equivalent to the maximum recommended daily intranasal dosage in children on a ug/sq m
basis) for 104 weeks.
from HSDB
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Two 18-month studies were performed in mice
to evaluate the carcinogenic potential of fluticasone propionate when given topically (as an 0.05% ointment) and
orally. No evidence of carcinogenicity was found in either study.

from HSDB
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Fluticasone propionate has been shown to
be teratogenic and embryotoxic in mice or rats when administered subcutaneously at daily dosages of 45 or 100
ug/kg, respectively (approximately equivalent to 4 times the maximum recommended daily intranasal dosage in
adults based on surface area). Observed fetal toxicity was characteristic of potent glucocorticoid compounds and
included embryonic growth retardation, omphalocele, cleft palate, and retarded cranial ossification. ... Following
oral administration of up to 300 ug/kg (approximately 25 times the maximum recommended daily intranasal
dosage in adults on a ug/sq m basis) daily of fluticasone propionate in rabbits, the drug was not detected in
plasma, and no maternal effects nor increased incidence of external, visceral, or skeletal fetal defects was
detected. The low bioavailability and small distribution of fluticasone propionate across the placenta may
account for the lack of teratogenicity; in rats and rabbits receiving oral fluticasone propionate dosages of 100
ug/kg (590 ug/sq m) or 300 ug/kg (3.6 mg/sq m), respectively, less than 0.008% of the dose crossed the
placenta.
from HSDB
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Fetal weight reduction and cleft palate were
observed in offspring of rabbits given fluticasone propionate 4 ug/kg subcutaneously (less than the maximum
recommended daily intranasal dosage in adults).
from HSDB
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in rats using
subcutaneous fluticasone propionate at daily dosages of 50 ug/kg (approximately 2 times the maximum
recommended daily intranasal dosage in adults on a ug/sq m basis) have shown no evidence of impaired fertility.
However, prostate weight was substantially reduced in rats at a subcutaneous dose of 50 ug/kg.
from HSDB
/GENOTOXICITY/ No evidence of mutagenicity was observed in vitro in prokaryotic or eukaryotic cells when
fluticasone propionate was tested in in vitro studies including the Ames microbial (Salmonella typhimurium)
mutagen test, Escherichia coli fluctuation test, and Saccharomyces cerevisiae gene conversion test. When tested
in in vitro mammalian cell cytogenetic studies, including Chinese hamster ovary and cultured human peripheral
lymphocytes, fluticasone propionate did not appear to cause chromosomal damage. No evidence of adverse
chromosomal effects was observed in an in vivo micronucleus test in mice receiving high doses of fluticasone
propionate by the oral or subcutaneous routes. Furthermore, the drug did not delay erythroblast division in bone
marrow.
from HSDB
12.1.5 Populations at Special Risk

Pediatric patients may be more susceptible to systemic toxicity from equivalent doses /of topical fluticasone
propionate/ due to their larger skin surface to body mass ratios.
from HSDB
Parents of pediatric patients should be advised not to use this medication in the treatment of diaper dermatitis.
Fluticasone propionate cream should not be applied in the diaper areas as diapers or plastic pants may
constitute occlusive dressing.
from HSDB
12.1.6 Protein Binding

91%
from DrugBank
12.2 Ecological Information

12.2.1 Environmental Fate/Exposure Summary
Fluticasone's production and use in the production of fluticasone propionate may result in its release to the
environment through various waste streams. If released to air, an estimated vapor pressure of 7.4X10-13 mm Hg
at 25 deg C indicates fluticasone will exist solely in the particulate phase in the atmosphere. Particulate-phase
fluticasone will be removed from the atmosphere by wet or dry deposition. Fluticasone does not contain
chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct
photolysis by sunlight. If released to soil, fluticasone is expected to have moderate mobility based upon an
estimated Koc of 290. Volatilization from moist soil surfaces is not expected to be an important fate process
based upon an estimated Henry's Law constant of 2.3X10-9 atm-cu m/mole. Biodegradation data were not
available. If released into water, fluticasone is expected to adsorb to suspended solids and sediment based upon
the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon
this compound's estimated Henry's Law constant. An estimated BCF of 3 suggests the potential for
bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate
process since this compound lacks functional groups that hydrolyze under environmental conditions.
Occupational exposure to fluticasone may occur through inhalation and dermal contact with this compound at
workplaces where fluticasone is produced or used. Exposure to fluticasone among the general population may be
limited to those administered medications that contain fluticasone, such as Advair, an antiallergic. (SRC)
from HSDB
12.2.2 Artificial Sources

Fluticasone's production and use in the production of fluticasone propionate, an antiallergic, antiasthmatic, and
anti-inflammatory(1), may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 14th ed., Whitehouse Station, NJ: Merck and Co., Inc., p. 721 (2006)
from HSDB
12.2.3 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 290(SRC), determined from
a structure estimation method(2), indicates that fluticasone is expected to have moderate mobility in soil(SRC).
Volatilization of fluticasone from moist soil surfaces is not expected to be an important fate process(SRC) given
an estimated Henry's Law constant of 2.3X10-9 atm-cu m/mole(SRC), using a fragment constant estimation
method(3). Fluticasone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor
pressure of 7.4X10-13 mm Hg at 25 deg C(SRC), determined from a fragment constant method(4).
Biodegradation data were not available(SRC, 2009).
(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992) (3) Meylan WM,
Howard PH; Environ Toxicol Chem 10: 1283-93 (1991) (4) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I,
Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
from HSDB
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 290(SRC), determined from a
structure estimation method(2), indicates that fluticasone is expected to adsorb to suspended solids and
sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law
constant of 2.3X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4).
According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of 1.4(6) and a
regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC).
Biodegradation data were not available(SRC, 2009).
(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992) (3) Lyman WJ et al;
Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990) (4) Meylan
WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991) (5) Franke C et al; Chemosphere 29: 1501-14 (1994) (6) Meylan WM,
Howard PH; J Pharm Sci 84: 83-92 (1995) (7) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
from HSDB
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the
atmosphere(1), fluticasone, which has an estimated vapor pressure of 7.4X10-13 mm Hg at 25 deg C(SRC),
determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the
ambient atmosphere. Particulate-phase fluticasone may be removed from the air by wet or dry deposition(SRC).
Fluticasone does not contain chromophores that absorb at wavelengths >290 nm(3) and therefore is not
expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I,
Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985) (3)) Lyman WJ et al; Handbook of Chemical Property Estimation
Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)
from HSDB
12.2.4 Abiotic Degredation

Fluticasone is expected to undergo hydrolysis in the environment due to the presence of functional groups that
hydrolyze under environmental conditions(1). Fluticasone does not contain chromophores that absorb at
wavelengths >290 nm(1) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12
(1990)
from HSDB
12.2.5 Bioconcentration
An estimated BCF of 3 was calculated in fish for fluticasone(SRC), using an estimated log Kow of 1.4(1) and a
regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for
bioconcentration in aquatic organisms is low(SRC).
(1) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995) (2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999) (3)
Franke C et al; Chemosphere 29: 1501-14 (1994)
from HSDB
12.2.6 Soil Adsorption/Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of fluticasone can be
estimated to be 290(SRC). According to a classification scheme(2), this estimated Koc value suggests that
fluticasone is expected to moderate mobility in soil.

(1) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992) (2) Swann RL et al; Res Rev 85: 17-28 (1983)
from HSDB
12.2.7 Volatilization from Water/Soil

The Henry's Law constant for fluticasone is estimated as 2.3X10-9 atm-cu m/mole(SRC) using a fragment
constant estimation method(1). This Henry's Law constant indicates that fluticasone is expected to be essentially
nonvolatile from water surfaces(2). Fluticasone's Henry's Law constant indicates that volatilization from moist
soil surfaces may not occur(SRC). Fluticasone is not expected to volatilize from dry soil surfaces(SRC) based
upon an estimated vapor pressure of 7.4X10-13 mm Hg(SRC), determined from a fragment constant method(3).
(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991) (2) Lyman WJ et al; Handbook of Chemical Property
Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990) (3) Lyman WJ; p. 31 in Environmental Exposure
From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
from HSDB
12.2.8 Water Concentrations

While data specific to fluticasone were not located(SRC, 2009), the literature suggests that some
pharmaceutically active compounds originating from human and veterinary therapy are not eliminated
completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1).
Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic
waste compounds may be degrading to new and more persistent compounds that may be released instead of or
in addition to the parent compound(2).
(1) Heberer T; Tox Lett 131: 5-17 (2002) (2) Koplin DW et al; Environ Sci Toxicol 36: 1202-211 (2002)
from HSDB
12.2.9 Milk Concentrations

In lactating rats, subcutaneous administration of tritiated fluticasone propionate (10 ug/kg, approximately onethird the maximum recommended daily intranasal dosage in adults on a ug/sq m basis) resulted in measurable
radioactivity in both plasma and milk.
from HSDB
12.2.10 Probable Routes of Human Exposure

Occupational exposure to fluticasone may occur through inhalation and dermal contact with this compound at
workplaces where fluticasone is produced or used. Exposure to fluticasone among the general population may be
limited to those administered medications that contain fluticasone, such as Advair, an antiallergic. (SRC)
from HSDB
13 Literature
13.1 Depositor Provided PubMed Citations
Depositor Provided PubMed
Citations
1205 records
from PubChem
13.2 NLM Curated PubMed Citations

LOADING... PLEASE WAIT...
from PubChem
13.3 Synthesis References

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.
from DrugBank
14 Patents
2125667 Canada
from DrugBank
2317999 Canada
from DrugBank
7500444 United States
from DrugBank
RE40045
from DrugBank
14.1 Depositor-Supplied Patent Identifiers

from PubChem
15 Biomolecular Interactions and Pathways

15.1 DrugBank Interactions
DrugBank Interactions: 1 of 8
Enzyme
Action
Cytochrome P450 3A5

1. substrate
2. inhibitor
General Function
Secondary metabolites biosynthesis, transport and catabolism
Specific Function
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
Gene Name
CYP3A5
GenBank Gene
J04813
GenBank Protein
181346
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
References
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
from DrugBank
Enzyme
Cytochrome P450 3A7
Action
substrate
General Function
Secondary metabolites biosynthesis, transport and catabolism
Specific Function

transport pathway. It oxidizes a variety of structurally unrelated compounds,
including steroids, fatty acids, and xenobiotics
Gene Name
CYP3A7
GenBank Gene
D00408
GenBank Protein
220149
References
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
from DrugBank
Carrier
Corticosteroid-binding globulin
General Function
Involved in serine-type endopeptidase inhibitor activity
Specific Function
Major transport protein for glucocorticoids and progestins in the blood of

almost all vertebrate species
Gene Name
SERPINA6
GenBank Gene
J02943
GenBank Protein
179971
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
References
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
from DrugBank
Enzyme
Action
Cytochrome P450 3A4

1. substrate
2. inhibitor
General Function
Involved in monooxygenase activity
Specific Function

transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and
midazolam 4- hydroxylation) of structurally unrelated compounds, including
steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates
etoposide
Gene Name
CYP3A4
GenBank Gene
M18907
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
References
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
from DrugBank
Target
Glucocorticoid receptor
Action
agonist
General Function
Involved in DNA binding
Specific Function
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
Gene Name
NR3C1
GenBank Gene
X03225
GenBank Protein
31680
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):595600. 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
References
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
from DrugBank
Target
Progesterone receptor
Action
agonist
General Function
Involved in transcription factor activity
Specific Function
The steroid hormones and their receptors are involved in the regulation of
eukaryotic gene expression and affect cellular proliferation and differentiation
in target tissues
Gene Name
PGR
GenBank Gene
X51730
GenBank Protein
35652
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
from DrugBank
Target
Mineralocorticoid receptor
Action
antagonist
General Function
Carbohydrate transport and metabolism
Specific Function
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
Gene Name
NR3C2
GenBank Gene
M16801
GenBank Protein
307166
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
from DrugBank
Target
Cytosolic phospholipase A2
Action
inhibitor
General Function
Involved in phospholipase activity
Specific Function
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
Gene Name
PLA2G4A
GenBank Gene
M72393
GenBank Protein
190007
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
from DrugBank
16 Biological Test Results

16.1 BioAssay Results
Refine/Analyze
1 to 10 of 251
3 ... 26
Download
Relevance
Activity
Substance
BioAssay
inactive
49681696
uHTS for identification of Inhibitors of Mdm2/MdmX interaction in luminescent

format. [AID: 485346]
inactive
EC50
49681696
Screen for small molecule probes relevant to Friedreich's ataxia, Single Dose
and Dose Response [AID: 1465]
active
IC50: 0.0001M
103539175
Inhibition of TNFalpha release in human PBMC by ELISA assay [AID: 622346]
active
IC50: 0.0093M
103539175
Inhibition of TNFalpha release in LPS-stimulated human whole blood by ELISA

assay [AID: 622347]
unspecified
103539175
Metabolic stability of compound in human liver microsomes assessed as

intrinsic clearance by equilibrium dialysis [AID: 622348]
unspecified
103539175
Metabolic stability of compound in human liver microsomes assessed as

unbound intrinsic clearance by equilibrium dialysis [AID: 622349]
unspecified
103539175
Metabolic stability in human liver microsomes assessed as phase 2

glucuronidation in presence of UDPGA [AID: 622350]
unspecified
103539175
Clearance in rat at 0.5 mg/kg, iv [AID: 622351]
unspecified
103539175
Unbound clearance in rat at 0.5 mg/kg, iv [AID: 622353]
unspecified
103539175
Oral bioavailability in rat at 2 mg/kg [AID: 622355]

from PubChem
17 Classification
17.1 Ontologies
17.1.1 MeSH Tree
Refine/Analyze
1 to 1 of 1
List View
Download
Tree View
fluticasone
from MeSH
17.1.2 ChEBI Ontology

Refine/Analyze
1 to 1 of 1
List View
Download
Tree View
fluticasone propionate
from ChEBI
17.1.3 Gene Ontology: Biological Process

from Gene Ontology
17.1.4 Gene Ontology: Molecular Function

from Gene Ontology
17.1.5 KEGG: Drug

17.1.6 KEGG: USP
from KEGG
from KEGG
17.1.7 KEGG: ATC

from KEGG
17.1.8 KEGG: CYP

from KEGG
17.1.9 KEGG: Target-based Classification of Drugs

from KEGG
17.1.10 WIPO IPC

from WIPO
18 Information Sources
1. ECHA 617-082-4 http://echa.europa.eu/
2. Fluticasone from HSDB 7740 http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?
dbs+hsdb:@term+@rn+@rel+90566-53-3
3. Fluticasone Propionate from DrugBank DB00588 http://www.drugbank.ca/drugs/DB00588
4. DrugBank DB00588 interaction #6 http://www.drugbank.ca/drugs/DB00588#enzymes
7. DrugBank DB00588 interaction #1 http://www.drugbank.ca/drugs/DB00588#targets
11. DrugBank DB00588 interaction #8 http://www.drugbank.ca/drugs/DB00588#carriers
12. Fluticasone Propionate from NCIt C29061_2912 http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?
dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C29061
NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational
and basic research, and public information and administrative activities.
13. The Cambridge Structural Database CCDC 735705 http://www.ccdc.cam.ac.uk/pages/Home.aspx

The Cambridge Structural Database provides access to 3D structures of molecules determined experimentally using
diffraction techniques.
14. The Cambridge Structural Database CCDC 290181 http://www.ccdc.cam.ac.uk/pages/Home.aspx

The Cambridge Structural Database provides access to 3D structures of molecules determined experimentally using
diffraction techniques.
15. Cutivate from FDA Drugs, DailyMed, and PubMed Health 981
16. Flonase from FDA Drugs, DailyMed, and PubMed Health 1567
17. Flovent diskus 100 from FDA Drugs, DailyMed, and PubMed Health 1568
20. Flovent hfa from FDA Drugs, DailyMed, and PubMed Health 1571
21. Fluticasone propionate from FDA Drugs, DailyMed, and PubMed Health 1612
22. FDA/SPL Indexing data O2GMZ0LF5W
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm377913.htm
23. PubChem http://pubchem.ncbi.nlm.nih.gov
Data deposited in or computed by PubChem
24. fluticasone from MeSH 67065382 http://www.ncbi.nlm.nih.gov/mesh/67065382

25. MeSH Tree from MeSH DescTree http://www.nlm.nih.gov/mesh/meshhome.html
MeSH (Medical Subject Headings) is the NLM controlled vocabulary thesaurus used for indexing articles for PubMed.
26. ChEBI Ontology from ChEBI OBO http://www.ebi.ac.uk/chebi/userManualForward.do#ChEBI%20Ontology

The ChEBI Ontology is a structured classification of the entities contained within ChEBI.
27. Drug from KEGG br08301 http://www.genome.jp/dbget-bin/www_bget?brite:br08301

Therapeutic category of drugs in Japan
28. USP from KEGG br08302 http://www.genome.jp/dbget-bin/www_bget?brite:br08302

USP Drug Classification
29. ATC from KEGG br08303 http://www.genome.jp/dbget-bin/www_bget?brite:br08303

Anatomical Therapeutic Chemical (ATC) classification
30. KEGG br08310 http://www.genome.jp/dbget-bin/www_bget?brite:br08310

Target-based classification of drugs
31. biological process from Gene Ontology GO_ROOT_486550
http://amigo.geneontology.org/amigo/term/GO:0008150
The Gene Ontology (GO) http://www.geneontology.org/ project provides a controlled vocabulary of terms for describing the
functions of gene products, and is divided into three domains. Each term in the biological processes domain, shown here,
represents recognized series of events, or a collection of molecular events with a defined beginning and end. Mutant
phenotypes often reflect disruptions in biological processes. The terms below apply to the gene/protein target(s) tested by
the BioAssay.
32. molecular function from Gene Ontology GO_ROOT_486552

http://amigo.geneontology.org/amigo/term/GO:0003674
The Gene Ontology (GO) http://www.geneontology.org/ project provides a controlled vocabulary of terms for describing the
functions of gene products, and is divided into three domains. Each term in the molecular functions domain, shown here,
represent a protein's jobs or abilities. These may include transporting things around, binding to things, holding things
together and changing one thing into another. This is different from the biological processes the gene product is involved in,
which involve more than one activity. The terms below apply to the gene/protein target(s) tested by the BioAssay.
33. International Patent Classification 2015 from WIPO IPC http://www.wipo.int/classifications/ipc/

The World Intellectual Property Organization (WIPO) International Patent Classification (IPC) provides for a hierarchical
system of language independent symbols for the classification of patents and utility models according to the different areas
of technology to which they pertain.
34. CYP from KEGG br08309 http://www.genome.jp/dbget-bin/www_bget?brite:br08309

Cytochrome P450 interactions
35. Dermatologic Agents from MeSH 68003879 http://www.ncbi.nlm.nih.gov/mesh/68003879

36. Anti-Inflammatory Agents from MeSH 68000893 http://www.ncbi.nlm.nih.gov/mesh/68000893
37. Bronchodilator Agents from MeSH 68001993 http://www.ncbi.nlm.nih.gov/mesh/68001993
38. Anti-Allergic Agents from MeSH 68018926 http://www.ncbi.nlm.nih.gov/mesh/68018926

Fluticasone Propionate - C25h31f3o5s - Pubchem

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NIH

U.S. National Library of Medicine

National Center for Biotechnology Information

PUBCHEM COMPOUND FLUTICASONE PROPIONATE

Cite this Record

Flixonase; Flixotide; More...

3 Names and Identifiers

3.1.3 InChI Key

3.1.4 Canonical SMILES

3.1.5 Isomeric SMILES

3.2 Other Identifiers

3.3.2 Depositor-Supplied Synonyms

31. Cutivate (TN)

32. Flixonase Nasal Spray

13. Flovent Diskus 50

14. Flovent Diskus 100

15. Flovent Diskus 250

26. Flixotide Disks

27. Flixotide Disk

37. Fluticasonpropionat Allen

28. Flovent Diskus

38. Flonase (TN)

39. Flovent (TN)

30. Flixotide Inhaler

4 Chemical and Physical Properties

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Topological Polar Surface Area

Heavy Atom Count

Isotope Atom Count

Defined Atom Stereocenter Count

Undefined Atom Stereocenter Count

Defined Bond Stereocenter Count

Undefined Bond Stereocenter Count

Covalently-Bonded Unit Count

4.2 Experimental Properties

4.2.3 Vapor Pressure

4.3 Crystal Structures

Crystal Structure Data

Crystal Structure Data

5.2 Related Compounds

Same Parent, Connectivity

Same Parent, Stereo

Same Parent, Isotope

Same Parent, Exact

Mixtures, Components, and

5.3.2 Substances by Category

Chemical Vendors (27)

5.4 Entrez Crosslinks

A&J Pharmtech CO., LTD.

AKos Consulting & Solutions

Hangzhou APIChem Technology

Finetech Industry Limited

7 Drug and Medication Information

Cutivate (from Drugs@FDA)

Anti-Inflammatory, Corticosteroid, Intermediate, Corticosteroid, Strong (from

CUTIVATE (fluticasone propionate cream) Cream, 0.05% contains fluticasone

7300669 (from FDA Orange Book)

Flonase (from Drugs@FDA)

Fluticasone propionate, the active component of FLONASE Nasal Spray, is a

Flovent diskus 100 (from Drugs@FDA)

5873360*PED; 5873360 (from FDA Orange Book)

7500444PED; 5674472; 6966467; 5658549PED; 6170717*PED; 6997349;