Identification
- Summary
Difluocortolone is a topical corticosteroid used for the symptomatic treatment of inflammatory skin disorders like eczema, seborrheic eczema, lichen planus and psoriasis.
- Generic Name
- Difluocortolone
- DrugBank Accession Number
- DB09095
- Background
Difluocortolone is a potent topical corticosteroid. It is commonly used in dermatology for the reduction of inflammation and itching. It was submitted to the FDA in July 1984 by the pharmaceutical company Schering AG.3
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
Structure for Difluocortolone (DB09095)
- Weight
- Average: 394.459
Monoisotopic: 394.195565708 - Chemical Formula
- C22H28F2O4
- Synonyms
- Diflucortolona
- Diflucortolone
- Diflucortolonum
Pharmacology
- Indication
Difluocortolone is used as a topical treatment of the symptoms of inflammatory skin disorders like eczema, seborrheic eczema, lichen planus and psoriasis. All these disorders present as a common characteristic the occurrence of symptoms as itching, swelling, redness and scaling.4
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Gingivitis Combination Product in combination with: Josamycin (DB01321) •••••••••••• ••••• •••••••• Used in combination to treat Infectious periodontal diseases Combination Product in combination with: Josamycin (DB01321) •••••••••••• ••••• •••••••• Used in combination to treat Periodontitis Combination Product in combination with: Josamycin (DB01321) •••••••••••• ••••• •••••••• Used in combination for symptomatic treatment of Skin inflammation Combination Product in combination with: Isoconazole (DB08943) •••••••••••• ••••• ••••• Used in combination to treat Stomatitis Combination Product in combination with: Josamycin (DB01321) •••••••••••• ••••• •••••••• - Contraindications & Blackbox Warnings
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Diflucortolone is a steroid with the properties of being an anti-inflammatory, antipruritic and vasoconstrictive.1 Its activity causes the vasoconstriction of the blood vessels and thus a decrease in the release of inflammatory substances. These actions produce the effect of skin soothed and elimination of the symptoms.4
- Mechanism of action
Diflucortolone performs its action by the induction of lipocortins which are phospholipase A2 inhibitory proteins and sequentially inhibiting the release of arachidonic acid. The absence of arachidonic acid translates to the inhibition of the formation, release and activity of endogenous chemical inflammatory mediators. Another mechanism of action is the transrepression in which diflucortolone binds to the glucocorticoid receptor which induces its migration to the nucleus where it stimulates the transcription of anti-inflammatory genes like tyrosine aminotransferase, phophoenolpyruvate carboxykinase, IL-10, etc. and suppress the expression of proinflammatory genes like cytokines, growth factors, adhesion molecules, etc.1
Target Actions Organism AAnnexin A3 inducerHumans AGlucocorticoid receptor binderHumans - Absorption
The absorption of diflucortolone is made mainly percutaneously but it may be absorbed systemically. The absorption and bioavailability of diflucortolone will be related to the type of formulation found in the medication.1 The percutaneous absorption depends on the vehicle, dose, treatment area, duration of treatment, the condition of treatment, the status of penetration barrier and localization of treated area in the body.6 Thus, rectal administration of diflucortolone produces a slow and low absorption with an AUC, Cmax and Tmax of 10.8 ng h/ml, 0.75 ng/ml and 4.7 h, respectively.5
- Volume of distribution
Less of 1% of the administered dose reaches systemic circulation.7 In order to exert its functions, diflucortolone has to distribute into the living epidermis and upper dermis. Reports have shown that the skin absorption of diflucortolone is rapid where the absorption gets significantly increased in damaged skin. Diflucortolone gets percutaneously absorbed and distributed into organs and tissues where it will be metabolized. When diflucortolone in an ointment form is applied in healthy skin 0.7% of the administered dose is percutaneously absorbed after a 7-hour exposure.6
- Protein binding
Diflucortolone gets rapidly metabolized and eliminated, thus there is a very limited circulation of the unchanged drug in blood plasma.6 Actually, the percutaneous absorption is so low that less than 1% of the admministered dose reaches systemyc circulation.7
- Metabolism
The metabolism of diflucortolone is done in the liver where it is very rapidly degraded. After 5 minutes of administration of diflucortolone in a dose of 1mg, there is a concentration of intact diflucortolone in plasma of 6-8 ng/ml. The analysis of the metabolites showed the presence of 11-keto-diflucortolone as the major metabolite in the plasma.2
- Route of elimination
The elimination of diflucortolone is rapid and complete. After 24 hours of dose administration 56% of the dose was eliminated by the urine and after 7 days 98% of the administered dose was recovered. The excretion of diflucortolone is subdivided in urine which accounts for 75% of the administered dose and in feces that accounts for the other 25% of the administered dose. From the eliminated dose, 30% was formed by unconjugated steroids, 20% as steroid-glucuronides and 10% as steroid-sulfates.2
- Half-life
The half-life of diflucortolone is approximately in the range of 4 to 5 h while the half-life of 3H-diflucortolone valerate is approximately 9 h.2
- Clearance
Diflucortolone gets rapidly eliminated and the metabolites produced are the latest in getting eliminated from the body.6
- Adverse Effects
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Diflucortolone can cause skin irritation, vesicles or red patches on the skin.4
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Difluocortolone which could result in a higher serum level. Abametapir The serum concentration of Difluocortolone can be increased when it is combined with Abametapir. Abatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Difluocortolone. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Difluocortolone. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Difluocortolone. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Difluocortolone valerate 1A63Z067C8 59198-70-8 HHJIUUAMYGBVSD-YTFFSALGSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Nerisone Cream Cream 0.1 % Topical Glaxosmithkline Inc 1983-12-31 2016-07-12 Canada 
Nerisone Oily Cream Cream 0.1 % Topical Glaxosmithkline Inc 1983-12-31 2016-09-30 Canada Nerisone Ointment Ointment 0.1 % Topical Glaxosmithkline Inc 1983-12-31 2015-11-03 Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ALBACORT % 1+% 0.1 KREM, 15 G Difluocortolone valerate (1 mg/g) + Isoconazole nitrate (10 mg/g) Cream Topical KENTFARMA İLAÇ A.Ş. 2018-03-27 Not applicable Turkey 
FUGGY % 0.1 + % 1 KREM, 15 G Difluocortolone valerate (0.1 %) + Isoconazole nitrate (1 %) Cream Topical TRIPHARMA İLAÇ SAN. VE TİC. A.Ş. 2019-09-13 Not applicable Turkey FUGGY % 0.1 + % 1 KREM, 30 G Difluocortolone valerate (0.1 %) + Isoconazole nitrate (1 %) Cream Topical TRIPHARMA İLAÇ SAN. VE TİC. A.Ş. 2020-08-14 Not applicable Turkey FUGİSİD %1 + %0,1 KREM, 15 G Difluocortolone valerate (0.1 %) + Isoconazole nitrate (1 %) Cream Topical İSTANBUL İLAÇ SAN. VE TİC. A.Ş. 2019-01-10 Not applicable Turkey FUNGOID %1+ %0,1 KREM, 15 G Difluocortolone (0.1 %) + Isoconazole nitrate (1 %) Cream Topical SAĞLIK ÜRÜN VE HİZMETLERİ TİC. LTD. ŞTİ. 2016-11-14 Not applicable Turkey
Categories
- ATC Codes
- D07AC06 — Diflucortolone
- D07AC — Corticosteroids, potent (group III)
- D07A — CORTICOSTEROIDS, PLAIN
- D07 — CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS
- D — DERMATOLOGICALS
- D07XC — Corticosteroids, potent, other combinations
- D07X — CORTICOSTEROIDS, OTHER COMBINATIONS
- D07 — CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS
- D — DERMATOLOGICALS
- Drug Categories
- Adrenal Cortex Hormones
- Anti-Inflammatory Agents
- Corticosteroids
- Corticosteroids, Dermatological Preparations
- Corticosteroids, Potent (Group III)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inducers
- Cytochrome P-450 CYP3A5 Inducers (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Substrates
- Dermatologicals
- Drugs that are Mainly Renally Excreted
- Fused-Ring Compounds
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hyperglycemia-Associated Agents
- Immunosuppressive Agents
- Pregnadienediols
- Pregnadienes
- Pregnanes
- Steroids
- Steroids, Fluorinated
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 21-hydroxysteroids. These are steroids carrying a hydroxyl group at the 21-position of the steroid backbone.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Hydroxysteroids
- Direct Parent
- 21-hydroxysteroids
- Alternative Parents
- Gluco/mineralocorticoids, progestogins and derivatives / 20-oxosteroids / 11-beta-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Alpha-hydroxy ketones / Secondary alcohols / Cyclic alcohols and derivatives / Cyclic ketones show 6 more
- Substituents
- 11-beta-hydroxysteroid / 11-hydroxysteroid / 20-oxosteroid / 21-hydroxysteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 6-halo-steroid / 9-halo-steroid / Alcohol / Aliphatic homopolycyclic compound show 22 more
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- K253365DXI
- CAS number
- 2607-06-9
- InChI Key
- OGPWIDANBSLJPC-RFPWEZLHSA-N
- InChI
- InChI=1S/C22H28F2O4/c1-11-6-13-14-8-16(23)15-7-12(26)4-5-21(15,3)22(14,24)18(28)9-20(13,2)19(11)17(27)10-25/h4-5,7,11,13-14,16,18-19,25,28H,6,8-10H2,1-3H3/t11-,13+,14+,16+,18+,19-,20+,21+,22+/m1/s1
- IUPAC Name
- (1S,2R,3aS,3bS,5S,9aS,9bR,10S,11aS)-5,9b-difluoro-10-hydroxy-1-(2-hydroxyacetyl)-2,9a,11a-trimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-one
- SMILES
- [H][C@@]12C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C
References
- General References
- Uva L, Miguel D, Pinheiro C, Antunes J, Cruz D, Ferreira J, Filipe P: Mechanisms of action of topical corticosteroids in psoriasis. Int J Endocrinol. 2012;2012:561018. doi: 10.1155/2012/561018. Epub 2012 Nov 5. [Article]
- Mutzel VW: [Pharmacokinetics and biotransformation of diflucortolone valerate in man (author's transl)]. Arzneimittelforschung. 1976;26(7b):1487-92. [Article]
- FDA Submission [Link]
- Dokteronline [Link]
- J-stage papers [Link]
- Diflucortolone monograph [Link]
- Medicine.ie [Link]
- External Links
- PubChem Compound
- 11954369
- PubChem Substance
- 310265022
- ChemSpider
- 10128664
- 3392
- ChEBI
- 135624
- ChEMBL
- CHEMBL509924
- ZINC
- ZINC000004212939
- Wikipedia
- Diflucortolone
- MSDS
- Download (114 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Unknown Status Treatment Acute Respiratory Distress Syndrome (ARDS) / Adrenal Insufficiency 1 2 Active Not Recruiting Treatment Immediate Implants 1 1 Completed Treatment Cleft of Alveolar Ridge 1 Not Available Completed Not Available Atopic Dermatitis 1 Not Available Completed Not Available Relationship Between the Exposure of Glucocorticoids During Pregnancy and Orofacial Cleft Development 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Oral Cream Cutaneous 0.1 % Ointment Cutaneous 30 G Cream Cutaneous 0.3 % Cream Cutaneous Cream Cutaneous Ointment Topical 0.3 % Ointment 10 g Cream Cream Topical 1 mg/g Ointment 1 mg/g Solution Topical 0.1 % Cream Topical Ointment Cream Topical 0.1 % Ointment Topical 0.1 % Cream Cutaneous 1 MG/G Cream Cutaneous 3 MG/G Ointment 0.1 % Ointment 0.3 % Cream 01 % Ointment 01 % Cream Topical 1 mg/g - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 220ºC 'MSDS' boiling point (°C) 534ºC at 760 mmHg 'MSDS' water solubility 2.030 mg/L Lamparczyk H. CRC Handbook of Chromatography. (1992) logP 3.86 Lamparczyk H. CRC Handbook of Chromatography. (1992) - Predicted Properties
Property Value Source Water Solubility 0.0446 mg/mL ALOGPS logP 2.22 ALOGPS logP 2.01 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 13.42 Chemaxon pKa (Strongest Basic) -3.3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 74.6 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 100.99 m3·mol-1 Chemaxon Polarizability 40.2 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a6r-0009000000-619b96f4b8d9f9176603 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-03du-0009000000-e0bbef165cb8561b6420 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0296-0009000000-ec1b3531de2713b6e8d8 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-054k-0129000000-a343bb3cb95345fdc979 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-014r-0639000000-562d439634c1793f90e8 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-052o-1984000000-21c880428cada1f0528c Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 191.80287 predictedDeepCCS 1.0 (2019) [M+H]+ 193.69826 predictedDeepCCS 1.0 (2019) [M+Na]+ 199.7553 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Phospholipase a2 inhibitor activity
- Specific Function
- Inhibitor of phospholipase A2, also possesses anti-coagulant properties. Also cleaves the cyclic bond of inositol 1,2-cyclic phosphate to form inositol 1-phosphate.
- Gene Name
- ANXA3
- Uniprot ID
- P12429
- Uniprot Name
- Annexin A3
- Molecular Weight
- 36374.85 Da
References
- Uva L, Miguel D, Pinheiro C, Antunes J, Cruz D, Ferreira J, Filipe P: Mechanisms of action of topical corticosteroids in psoriasis. Int J Endocrinol. 2012;2012:561018. doi: 10.1155/2012/561018. Epub 2012 Nov 5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- 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
- Uva L, Miguel D, Pinheiro C, Antunes J, Cruz D, Ferreira J, Filipe P: Mechanisms of action of topical corticosteroids in psoriasis. Int J Endocrinol. 2012;2012:561018. doi: 10.1155/2012/561018. Epub 2012 Nov 5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInducer
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxygen binding
- 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 un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
Drug created at September 16, 2015 17:59 / Updated at December 02, 2023 07:01