Identification

Name
Clobetasone
Accession Number
DB13158
Type
Small Molecule
Groups
Approved
Description

Clobetasone is a corticosteroid used in dermatology, for treating such skin inflammation as seen in eczema, psoriasis and other forms of dermatitis, and ophthalmology. Topical clobetasone butyrate has shown minimal suppression of the Hypothalamic-pituitary-adrenal axis.

Structure
Thumb
Synonyms
  • Clobetasona
Product Ingredients
IngredientUNIICASInChI Key
Clobetasone butyrate8U0H6XI6EO25122-57-0FBRAWBYQGRLCEK-AVVSTMBFSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EumovateOintment0.05 %TopicalGlaxosmithkline Inc2001-06-252007-08-02Canada
Eumovate Ont 0.05%Ointment0.05 %TopicalGlaxo Canada Inc1979-12-312001-08-01Canada
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Eumovate Crm 0.05%Cream0.05 %TopicalGlaxo Canada Inc1979-12-312000-08-02Canada
Spectro Eczemacare Medicated CreamCream0.05 %TopicalGlaxosmithkline Inc1999-09-27Not applicableCanada
International/Other Brands
Eumosone (GlaxoSmithKline) / Eumovate (GlaxoSmithKline)
Categories
UNII
LT69WY1J6D
CAS number
54063-32-0
Weight
Average: 408.89
Monoisotopic: 408.1503652
Chemical Formula
C22H26ClFO4
InChI Key
XXIFVOHLGBURIG-OZCCCYNHSA-N
InChI
InChI=1S/C22H26ClFO4/c1-12-8-16-15-5-4-13-9-14(25)6-7-19(13,2)21(15,24)17(26)10-20(16,3)22(12,28)18(27)11-23/h6-7,9,12,15-16,28H,4-5,8,10-11H2,1-3H3/t12-,15-,16-,19-,20-,21-,22-/m0/s1
IUPAC Name
(1R,2S,10S,11S,13S,14R,15S)-14-(2-chloroacetyl)-1-fluoro-14-hydroxy-2,13,15-trimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-diene-5,17-dione
SMILES
[H][C@]1(C)C[C@@]2([H])[C@]3([H])CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)C(=O)C[C@]2(C)[C@@]1(O)C(=O)CCl

Pharmacology

Indication

In dermatology, topical clobestasone butyrate helps to reduce the itchiness and erythema associated with eczema and dermatitis. In ophthalmology, clobetasone butyrate 0.1% eye drops have been shown to be safe and effective in the treatment of dry eyes in Sjögren's Syndrome.

Associated Conditions
Pharmacodynamics

Topical corticosteroid like clobetasone are synthetic derivatives of cortisone which produce anti-inflammatory, antiproliferative, immunosuppressive and vasoconstrictor effects when applied to the skin.

Mechanism of action

Topically applied clobeyasone are thought to bind with cytoplasmic receptors in the dermal and intradermal cells and to induce inhibitory proteins, thus leading to decreased activity of prostaglandins, kinins, histamine, liposomal enzymes and other endogenous mediators of inflammation. Topical corticosteroids inhibit the migration of macrophages and leukocytes into areas of inflamed skin by reversing vascular dilation and permeability, resulting in decreased erythema, edema and pruritus.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
Absorption

Absorption is dependent on many drug-related factors including: intrinsic properties of the steroid itself; concentration of the drug (increased concentration generally leads to more drug being absorbed but may plateau at higher concentrations); vehicle used (optimized or augmented vehicles > ointments or gels > creams or lotions); duration of exposure; frequency of application; combination with other products that break down the skin barrier and increase absorption (e.g., salicylic acid, urea). Patient-related factors that influence absorption include: patient age (infants and children absorb topical medications more quickly and to a greater degree than adults, and have a greater total skin surface to body weight ratio; the elderly have thinner skin and absorb drug more readily); disruption of the skin due to inflammation or disease (e.g., absorption increased in atopic dermatitis); total skin area treated; skin site treated (absorption is much greater from thin-skinned areas such as scalp, face, eyelid, axilla, and scrotum than from areas with thicker skin such as forearm, knee, elbow, palm and sole); absorption is increased with increased temperature or humidity of the skin or the environment; occlusion of the treated skin (via plastic wrap, oily vehicles, dressings, tape, diapers, tight-fitting clothing, etc.) can increase absorption up to 10-fold.

Volume of distribution

The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary due to the fact that circulating levels are well below the level of detection.

Protein binding
Not Available
Metabolism

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolised, primarily in the liver.

Route of elimination

Clobetasone and its metabolites are excreted in urine.

Half life

N/A

Clearance
Not Available
Toxicity

Organism : Mouse Test type: LD50 Oral (Reported dose: >6gm/kg) LD50 Subcutaneous ( >3600mg/kg ) Effects : Behavioral : somnolence ( general depressed activity ) Blood changes in spleen

Organism : Mouse Test type: LD50 Route: Intraperitoneal Reported dose: 500 mg/kg

LD50 rat : 1510mg/kg Intraperitoneal LD50 rat >6gm/kg Oral LD 50 rat : > 2600mg/kg subcutaneous

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Wikipedia [Link]
  2. Medsafe [Link]
  3. ChemIdplus [Link]
External Links
KEGG Drug
D07717
PubChem Compound
71387
PubChem Substance
347829268
ChemSpider
64482
Wikipedia
Clobetasone
ATC Codes
S01BA09 — ClobetasoneD07AB01 — ClobetasoneS01CA11 — Clobetasone and antiinfectives
AHFS Codes
  • 84:06.00 — Anti-inflammatory Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentDermatitis, Eczematous1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
OintmentTopical0.05 %
CreamTopical0.05 %
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00691 mg/mLALOGPS
logP2.88ALOGPS
logP3.6ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)12.49ChemAxon
pKa (Strongest Basic)-3.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.44 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity104.72 m3·mol-1ChemAxon
Polarizability41.36 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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

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-oxosteroids / 17-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Tertiary alcohols / Alpha-hydroxy ketones / Alpha-chloroketones / Cyclic ketones
show 7 more
Substituents
Progestogin-skeleton / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 9-halo-steroid / Halo-steroid / 17-hydroxysteroid / Hydroxysteroid / Oxosteroid / 11-oxosteroid
show 21 more
Molecular Framework
Aliphatic homopolycyclic 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. UniProt [Link]
  2. KEGG [Link]

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. Eumovate cream monograph [File]

Drug created on December 04, 2016 20:58 / Updated on November 16, 2018 11:29