Difluocortolone

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Approved, Investigational, Withdrawn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

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Difluocortolone (DB09095)

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Weight

Average: 394.459
Monoisotopic: 394.195565708

Chemical Formula

C₂₂H₂₈F₂O₄

Synonyms

• Diflucortolona
• Diflucortolone
• Diflucortolonum

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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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Associated Conditions

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)	••••••••••••	•••••		••••••••

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Pharmacodynamics

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	inducer	Humans
AGlucocorticoid receptor	binder	Humans

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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Toxicity

Diflucortolone can cause skin irritation, vesicles or red patches on the skin.⁴

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Integrate drug-drug interactions in your software
Abacavir	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.

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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
Nerisone Oily Cream	Cream	0.1 %	Topical	Glaxosmithkline Inc	1983-12-31	2016-09-30
Nerisone Ointment	Ointment	0.1 %	Topical	Glaxosmithkline Inc	1983-12-31	2015-11-03

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
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
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
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
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

Categories

ATC Codes

D07AC06 — Diflucortolone

• D07AC — Corticosteroids, potent (group III)
• D07A — CORTICOSTEROIDS, PLAIN
• D07 — CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS
• D — DERMATOLOGICALS

D07XC04 — Diflucortolone

• D07XC — Corticosteroids, potent, other combinations
• D07X — CORTICOSTEROIDS, OTHER COMBINATIONS
• D07 — CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS
• D — DERMATOLOGICALS

D07BC04 — Diflucortolone and antiseptics

• D07BC — Corticosteroids, potent, combinations with antiseptics
• D07B — CORTICOSTEROIDS, COMBINATIONS WITH ANTISEPTICS
• 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 / Fluorohydrins / Organic oxides / Primary alcohols / Organofluorides / Hydrocarbon derivatives / Alkyl fluorides

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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 / Alkyl fluoride / Alkyl halide / Alpha-hydroxy ketone / Carbonyl group / Cyclic alcohol / Cyclic ketone / Delta-1,4-steroid / Fluorohydrin / Halo-steroid / Halohydrin / Hydrocarbon derivative / Ketone / Organic oxide / Organic oxygen compound / Organofluoride / Organohalogen compound / Organooxygen compound / Oxosteroid / Pregnane-skeleton / Primary alcohol / Progestogin-skeleton / Secondary alcohol

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

1. 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]
2. Mutzel VW: [Pharmacokinetics and biotransformation of diflucortolone valerate in man (author's transl)]. Arzneimittelforschung. 1976;26(7b):1487-92. [Article]
3. FDA Submission [Link]
4. Dokteronline [Link]
5. J-stage papers [Link]
6. Diflucortolone monograph [Link]
7. Medicine.ie [Link]

External Links

PubChem Compound

11954369

PubChem Substance

310265022

ChemSpider

10128664

RxNav

3392

ChEBI

135624

ChEMBL

CHEMBL509924

ZINC

ZINC000004212939

Wikipedia

Diflucortolone

MSDS

Download (114 KB)

Clinical Trials

Clinical Trials

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	predicted	DeepCCS 1.0 (2019)
[M+H]+	193.69826	predicted	DeepCCS 1.0 (2019)
[M+Na]+	199.7553	predicted	DeepCCS 1.0 (2019)

Targets

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Details1. Annexin A3

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

1. 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]

Details2. Glucocorticoid receptor

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

1. 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]

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Drug created at September 16, 2015 17:59 / Updated at December 02, 2023 07:01