Identification

Name
Fluocinonide
Accession Number
DB01047  (APRD00978)
Type
Small Molecule
Groups
Approved, Investigational
Description

A topical glucocorticoid used in the treatment of eczema.

Structure
Thumb
Synonyms
  • Fluocinonide
  • Fluocinonido
  • Fluocinonidum
External IDs
NSC-101791
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FluocinonideCream0.5 mg/1gTopicalPhysicians Total Care, Inc.1984-06-26Not applicableUs
FluocinonideSolution0.5 mg/1mLTopicalAlvogen Inc.2014-02-28Not applicableUs
FluocinonideCream0.5 mg/1gTopicalA S Medication Solutions1984-06-26Not applicableUs
FluocinonideCream0.5 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.1984-06-26Not applicableUs
FluocinonideCream0.5 mg/1gTopicalA-S Medication Solutions1984-06-262017-12-31Us
FluocinonideSolution0.5 mg/1mLTopicalCounty Line Pharamceuticals2014-02-28Not applicableUs
FluocinonideCream0.5 mg/1mLTopicalGolden State Medical Supply1984-06-26Not applicableUs
FluocinonideOintment0.05 mg/1gTopicalNucare Pharmaceuticals,inc.2016-09-06Not applicableUs
FluocinonideCream0.5 mg/1gTopicalLake Erie Medical Dba Quality Care Produts Llc1984-06-26Not applicableUs
FluocinonideOintment0.05 mg/1gTopicalCounty Line Pharamceuticals2016-09-06Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FluocinonideCream0.5 mg/1gTopicalMayne Pharma2016-10-01Not applicableUs
FluocinonideCream1 mg/1gTopicalAmneal Pharmaceuticals LLC2018-07-31Not applicableUs
FluocinonideSolution0.5 mg/1mLTopicalNovel Laboratories, Inc.2017-07-21Not applicableUs
FluocinonideCream0.5 mg/1gTopicalProficient Rx LP1984-06-26Not applicableUs
FluocinonideOintment0.5 mg/1gTopicalPhysicians Total Care, Inc.1994-11-22Not applicableUs
FluocinonideGel0.5 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.1997-07-29Not applicableUs
FluocinonideSolution0.5 mg/1mLTopicalE. Fougera & CO., A division of Fougera Pharmaceuticals Inc.1995-02-27Not applicableUs
FluocinonideOintment0.5 mg/1gTopicalE. Fougera & CO., A division of Fougera Pharmaceuticals Inc.1997-08-26Not applicableUs
FluocinonideSolution0.5 mg/1mLTopicalPhysicians Total Care, Inc.1993-05-28Not applicableUs
FluocinonideCream0.5 mg/1gTopicalA-S Medication Solutions1990-09-30Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Lidecomb CreamFluocinonide (0.5 mg) + Gramicidin D (0.25 mg) + Neomycin sulfate (5 mg) + Nystatin (100000 unit)CreamTopicalMedicis Pharmaceutical Corporation1980-12-311998-09-25Canada
International/Other Brands
Fluonex / Lidex (Medicis) / Lidex-E (Medicis) / Lonide / Lyderm (Taro) / Metosyn (Bioglan) / Topsymin / Topsyn (Syntex) / Vanos
Categories
UNII
2W4A77YPAN
CAS number
356-12-7
Weight
Average: 494.5249
Monoisotopic: 494.211609788
Chemical Formula
C26H32F2O7
InChI Key
WJOHZNCJWYWUJD-IUGZLZTKSA-N
InChI
InChI=1S/C26H32F2O7/c1-13(29)33-12-20(32)26-21(34-22(2,3)35-26)10-15-16-9-18(27)17-8-14(30)6-7-23(17,4)25(16,28)19(31)11-24(15,26)5/h6-8,15-16,18-19,21,31H,9-12H2,1-5H3/t15-,16-,18-,19-,21+,23-,24-,25-,26+/m0/s1
IUPAC Name
2-[(1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-6,6,9,13-tetramethyl-16-oxo-5,7-dioxapentacyclo[10.8.0.0²,⁹.0⁴,⁸.0¹³,¹⁸]icosa-14,17-dien-8-yl]-2-oxoethyl acetate
SMILES
[H][C@@]12C[C@@]3([H])[C@]4([H])C[C@]([H])(F)C5=CC(=O)C=C[C@]5(C)[C@@]4(F)[C@@H](O)C[C@]3(C)[C@@]1(OC(C)(C)O2)C(=O)COC(C)=O

Pharmacology

Indication

A topical anti-inflammatory product for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.

Associated Conditions
Pharmacodynamics

Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema. It relieves itching, redness, dryness, crusting, scaling, inflammation, and discomfort.

Mechanism of action

Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema. It relieves itching, redness, dryness, crusting, scaling, inflammation, and discomfort. Fluocinonide binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. Cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Like other glucocorticoid agents Fluocinolone acetonide acts as a physiological antagonist to insulin by decreasing glycogenesis (formation of glycogen). It also promotes the breakdown of lipids (lipolysis), and proteins, leading to the mobilization of extrahepatic amino acids and ketone bodies. This leads to increased circulating glucose concentrations (in the blood). There is also decreased glycogen formation in the liver.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
USmoothened homolog
agonist
Human
Absorption

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. In general, percutaneous absorption is minimal.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys.

Half life
Not Available
Clearance
Not Available
Toxicity

Side effects may include acne-like eruptions, burning, dryness, excessive hair growth, infection of the skin, irritation, itching, lack of skin colour, prickly heat, skin inflammation, skin loss or softening, stretch marks.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when (4R)-limonene is combined with Fluocinonide.
1,10-PhenanthrolineThe risk or severity of adverse effects can be increased when Fluocinonide is combined with 1,10-Phenanthroline.
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with Fluocinonide.
AcemetacinThe risk or severity of adverse effects can be increased when Acemetacin is combined with Fluocinonide.
AcetazolamideThe metabolism of Fluocinonide can be decreased when combined with Acetazolamide.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Fluocinonide.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Fluocinonide.
AlbendazoleThe metabolism of Fluocinonide can be decreased when combined with Albendazole.
AlclofenacThe risk or severity of adverse effects can be increased when Alclofenac is combined with Fluocinonide.
AlclometasoneThe risk or severity of adverse effects can be increased when Alclometasone is combined with Fluocinonide.
Food Interactions
Not Available

References

Synthesis Reference

US. Patent 3,197,469.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015181
KEGG Drug
D00325
PubChem Compound
9642
PubChem Substance
46504523
ChemSpider
9265
ChEBI
5109
ChEMBL
CHEMBL1501
Therapeutic Targets Database
DAP000421
PharmGKB
PA449664
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Fluocinonide
ATC Codes
D07CC05 — Fluocinonide and antibioticsD07AC08 — FluocinonideC05AA11 — Fluocinonide
AHFS Codes
  • 84:06.00 — Anti-inflammatory Agents
FDA label
Download (818 KB)
MSDS
Download (75.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedSupportive CareCarcinoma, Breast1
2CompletedTreatmentAtopic Dermatitis (AD)1
2TerminatedTreatmentHand-foot Skin Reaction / Rash1
4CompletedTreatmentAtopic Dermatitis (AD)1
4Unknown StatusTreatmentAtopic Dermatitis (AD)1
Not AvailableCompletedTreatmentPsoriasis1
Not AvailableNot Yet RecruitingTreatmentMycosis Fungoides (MF)1
Not AvailableRecruitingNot AvailableCutaneous Lupus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • A-S Medication Solutions LLC
  • Contract Pharm
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • E. Fougera and Co.
  • Gallipot
  • Innoviant Pharmacy Inc.
  • Major Pharmaceuticals
  • Mason Distributors
  • Medicis Pharmaceutical Co.
  • Nycomed Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patheon Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Qualitest
  • Quality Care
  • Rebel Distributors Corp.
  • Stat Rx Usa
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • United Research Laboratories Inc.
Dosage forms
FormRouteStrength
CreamTopical0.5 mg/1g
CreamTopical0.5 mg/1mL
GelTopical0.5 mg/1g
OintmentTopical0.05 mg/1g
OintmentTopical0.5 mg/1mL
OintmentTopical0.5 mg/1g
SolutionTopical.5 mg/1mL
SolutionTopical0.5 mg/1mL
CreamTopical
Cream; emulsionTopical.05 %
CreamTopical0.01 %
OintmentTopical0.01 %
OintmentTopical.05 %
GelTopical0.05 %
OintmentTopical0.05 %
CreamTopical.05 %
CreamTopical0.05 %
CreamTopical0.5 mg
JellyTopical.5 mg
CreamTopical1 mg/1g
Prices
Unit descriptionCostUnit
Vanos 0.1% Cream 60 gm Tube275.75USD tube
Fluocinonide powder176.0USD g
Vanos 0.1% Cream 30 gm Tube155.34USD tube
Fluocinonide 0.05% Ointment 60 gm Tube50.96USD tube
Fluocinonide 0.05% Gel 60 gm Tube50.78USD tube
Fluocinonide-E 0.05% Cream 60 gm Tube47.84USD tube
Fluocinonide 0.05% Gel 30 gm Tube30.1USD tube
Fluocinonide 0.05% Ointment 30 gm Tube28.61USD tube
Fluocinonide-E 0.05% Cream 30 gm Tube28.6USD tube
Fluocinonide 0.05% Solution 60ml Bottle27.23USD bottle
Fluocinonide 0.05% Cream 60 gm Tube22.71USD tube
Fluocinonide 0.05% Solution 20ml Bottle21.99USD bottle
Fluocinonide 0.05% Ointment 15 gm Tube21.88USD tube
Fluocinonide 0.05% Gel 15 gm Tube21.85USD tube
Fluocinonide-E 0.05% Cream 15 gm Tube20.18USD tube
Fluocinonide 0.05% Cream 30 gm Tube13.54USD tube
Fluocinonide 0.05% Cream 15 gm Tube11.99USD tube
Vanos 0.1% cream4.13USD g
Lidex 0.05% cream3.57USD g
Fluocinonide-e 0.05% cream1.33USD g
Fluocinonide 0.05% cream0.6USD g
Fluocinonide-emol 0.05% cream0.4USD g
Lyderm 0.05 % Gel0.38USD g
Lyderm 0.05 % Ointment0.37USD g
Lyderm 0.05 % Cream0.29USD g
Tiamol 0.05 % Emollient Cream0.27USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7220424No2003-01-072023-01-07Us
US7794738No2002-09-112022-09-11Us
US8232264No2003-03-092023-03-09Us
US6765001No2001-12-212021-12-21Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)309 °CPhysProp
water solubility4.74 mg/LNot Available
logP3.19HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0168 mg/mLALOGPS
logP2.93ALOGPS
logP2.05ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)13.55ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area99.13 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity120.56 m3·mol-1ChemAxon
Polarizability49.12 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9823
Blood Brain Barrier+0.981
Caco-2 permeable-0.5804
P-glycoprotein substrateSubstrate0.7813
P-glycoprotein inhibitor IInhibitor0.8103
P-glycoprotein inhibitor IINon-inhibitor0.5782
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateNon-substrate0.8667
CYP450 2D6 substrateNon-substrate0.8951
CYP450 3A4 substrateSubstrate0.7219
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9482
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8455
Ames testNon AMES toxic0.7768
CarcinogenicityNon-carcinogens0.9166
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.1492 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9835
hERG inhibition (predictor II)Non-inhibitor0.6907
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-05p9-0489400000-cb64b15c0db3ac6d9647

Taxonomy

Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 11-beta-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Alpha-acyloxy ketones / Ketals / 1,3-dioxolanes / Fluorohydrins / Cyclic ketones
show 9 more
Substituents
Progestogin-skeleton / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 9-halo-steroid / 6-halo-steroid / Halo-steroid / Hydroxysteroid / Oxosteroid / 11-beta-hydroxysteroid
show 28 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Jessop S, Whitelaw D, Jordaan F: Drugs for discoid lupus erythematosus. Cochrane Database Syst Rev. 2001;(1):CD002954. [PubMed:11279785]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Wnt-protein binding
Specific Function
G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought t...
Gene Name
SMO
Uniprot ID
Q99835
Uniprot Name
Smoothened homolog
Molecular Weight
86395.95 Da
References
  1. Wang J, Lu J, Bond MC, Chen M, Ren XR, Lyerly HK, Barak LS, Chen W: Identification of select glucocorticoids as Smoothened agonists: potential utility for regenerative medicine. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9323-8. doi: 10.1073/pnas.0910712107. Epub 2010 May 3. [PubMed:20439738]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Moore CD, Roberts JK, Orton CR, Murai T, Fidler TP, Reilly CA, Ward RM, Yost GS: Metabolic pathways of inhaled glucocorticoids by the CYP3A enzymes. Drug Metab Dispos. 2013 Feb;41(2):379-89. doi: 10.1124/dmd.112.046318. Epub 2012 Nov 9. [PubMed:23143891]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Steroid binding
Specific Function
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
Gene Name
SERPINA6
Uniprot ID
P08185
Uniprot Name
Corticosteroid-binding globulin
Molecular Weight
45140.49 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  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:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on October 15, 2018 04:36