Identification

Name
Cortisone acetate
Accession Number
DB01380
Type
Small Molecule
Groups
Approved, Investigational
Description

Cortisone acetate is a steroid hormone that has both glucocoriticoid and mineral corticoid activities. Corticosteroids are used to provide relief for inflamed areas of the body. They lessen swelling, redness, itching, and allergic reactions. They are often used as part of the treatment for a number of different diseases, such as severe allergies or skin problems, asthma, or arthritis. Endogenous glucocorticoids and some synthetic corticoids have high affinity to the protein transcortin (also called CBG, corticosteroid-binding protein), whereas all of them bind albumin. Glucocorticoids also bind to the cytosolic glucocorticoid receptor.

Structure
Thumb
Synonyms
  • Cortisyl
Active Moieties
NameKindUNIICASInChI Key
CortisoneprodrugV27W9254FZ53-06-5MFYSYFVPBJMHGN-ZPOLXVRWSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cortisone AcetateTablet5 mg/1OralUNSPECIFIED2006-01-04Not applicableUs
Cortisone AcetateTablet10 mg/1OralUNSPECIFIED2006-01-04Not applicableUs
Cortisone Acetate Tab 25mgTablet25 mgOralValeant Canada Lp Valeant Canada S.E.C.1973-12-31Not applicableCanada
Cortone Sus 50mg/mlSuspension50 mgIntramuscularMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1951-12-311999-08-06Canada
Cortone Tab 25mgTablet25 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1954-12-312002-07-29Canada
Cortone Tab 5mgTablet5 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1951-12-312002-07-29Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cortisone AcetateTablet25 mg/1OralWest Ward Pharmaceutical1972-06-13Not applicableUs00143 1202 01 nlmimage10 7a053d59
Cortisone AcetateTablet25 mg/1OralHikma Pharmaceutical2013-08-26Not applicableUs
Cortisone AcetateTablet25 mg/1OralWest-Ward Pharmaceuticals Corp2013-08-22Not applicableUs
Cortisone AcetateTablet25 mg/1OralGolden State Medical Supply1972-06-132017-01-02Us
International/Other Brands
Cortone acetate / Cortone Acetate (MSD)
Categories
UNII
883WKN7W8X
CAS number
50-04-4
Weight
Average: 402.4807
Monoisotopic: 402.204238692
Chemical Formula
C23H30O6
InChI Key
ITRJWOMZKQRYTA-RFZYENFJSA-N
InChI
InChI=1S/C23H30O6/c1-13(24)29-12-19(27)23(28)9-7-17-16-5-4-14-10-15(25)6-8-21(14,2)20(16)18(26)11-22(17,23)3/h10,16-17,20,28H,4-9,11-12H2,1-3H3/t16-,17-,20+,21-,22-,23-/m0/s1
IUPAC Name
2-[(1S,2R,10S,11S,14R,15S)-14-hydroxy-2,15-dimethyl-5,17-dioxotetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-14-yl]-2-oxoethyl acetate
SMILES
[H][C@@]12CC[C@](O)(C(=O)COC(C)=O)[C@@]1(C)CC(=O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C

Pharmacology

Indication

For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders.

Associated Conditions
Pharmacodynamics

As a glucocorticoid agent, cortisone acetate changes genetic transcription levels causing varied metabolic effects and a modified immune response to varied stimuli. lucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.

Mechanism of action

Cortisone acetate 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. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other 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.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
Absorption
Not Available
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. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

Half life
Not Available
Clearance
Not Available
Toxicity

Side effects include inhibition of bone formation, suppression of calcium absorption, delayed wound healing and hyperglycemia.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Cortisone acetate.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Cortisone acetate.
1-TestosteroneThe risk or severity of edema formation can be increased when 1-Testosterone is combined with Cortisone acetate.
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Cortisone acetate.
16-BromoepiandrosteroneThe risk or severity of edema formation can be increased when 16-Bromoepiandrosterone is combined with Cortisone acetate.
19-norandrostenedioneThe risk or severity of edema formation can be increased when 19-norandrostenedione is combined with Cortisone acetate.
1alpha-Hydroxyvitamin D5The therapeutic efficacy of 1alpha-Hydroxyvitamin D5 can be decreased when used in combination with Cortisone acetate.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Cortisone acetate is combined with 2-Methoxyethanol.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Cortisone acetate.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Cortisone acetate.
Food Interactions
Not Available

References

Synthesis Reference

Reichstein,T.; US. Patent 2,403,683; July 9, 1946. Gallagher,T.F.; US. Patent 2,447,325; August 17,1948; assigned to Research Corporation. Sarett, L.H.; U.S. Patent 2,541,104; February 13, 1951; assigned to Merck & Co., Inc.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015459
KEGG Drug
D00973
KEGG Compound
C08173
PubChem Compound
5745
PubChem Substance
46508852
ChemSpider
5543
BindingDB
50455157
ChEBI
3897
ChEMBL
CHEMBL1650
PharmGKB
PA449130
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cortisone_acetate
AHFS Codes
  • 68:04.00 — Adrenals
MSDS
Download (74.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentRotator Cuff Tear - Partial Thickness1
1CompletedTreatmentKnee Osteoarthritis (Knee OA)1
2CompletedTreatmentAngioedema1
2RecruitingTreatmentAdrenal Hyperplasia, Congenital1
2, 3RecruitingTreatmentOsteoarthritis of the Shoulder1
3RecruitingTreatmentAcute ACE-induced Angioedema1
3Unknown StatusTreatmentBack Pain Lower Back1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4CompletedTreatmentHip Injuries1
4RecruitingTreatmentCongenital Adrenal Hyperplasia (CAH)1
Not AvailableCompletedNot AvailableKnee Osteoarthritis (Knee OA)1
Not AvailableRecruitingTreatmentPlantar fascial fibromatosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bergen Brunswig
  • Consolidated Midland Corp.
  • CVS Pharmacy
  • Major Pharmaceuticals
  • Medicine Shop
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Pharmacia Inc.
  • Qualitest
  • West-Ward Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral10 mg/1
TabletOral25 mg/1
TabletOral5 mg/1
TabletOral25 mg
SuspensionIntramuscular50 mg
TabletOral5 mg
Prices
Unit descriptionCostUnit
Cortisone acetate powder24.18USD g
Cortisone Acetate 25 mg Tablet0.47USD tablet
Cortisone 25 mg tablet0.46USD tablet
Cortaid 1% cream0.21USD g
CVS Pharmacy cortisone 1% cream0.18USD g
CVS Pharmacy anti-itch 1% cream0.13USD g
Hydrocortisone 0.5% cream0.11USD g
Medi-cortisone 1% cream0.1USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)227-229Reichstein,T.; US. Patent 2,403,683; July 9, 1946. Gallagher,T.F.; US. Patent 2,447,325; August 17,1948; assigned to Research Corporation. Sarett, L.H.; U.S. Patent 2,541,104; February 13, 1951; assigned to Merck & Co., Inc.
water solubility20 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.10HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0278 mg/mLALOGPS
logP2.35ALOGPS
logP2.1ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)12.6ChemAxon
pKa (Strongest Basic)-3.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area97.74 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity105.63 m3·mol-1ChemAxon
Polarizability43.25 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.983
Blood Brain Barrier+0.9851
Caco-2 permeable-0.6606
P-glycoprotein substrateSubstrate0.7382
P-glycoprotein inhibitor IInhibitor0.7341
P-glycoprotein inhibitor IIInhibitor0.5925
Renal organic cation transporterNon-inhibitor0.7452
CYP450 2C9 substrateNon-substrate0.8551
CYP450 2D6 substrateNon-substrate0.9294
CYP450 3A4 substrateSubstrate0.7841
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9556
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8588
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9246
Ames testNon AMES toxic0.9409
CarcinogenicityNon-carcinogens0.9551
BiodegradationNot ready biodegradable0.9354
Rat acute toxicity2.1280 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9599
hERG inhibition (predictor II)Non-inhibitor0.6638
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0643900000-f8c82718aaac7d5f1097
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-2941000000-b0ec70aa310131ced784

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 / 3-oxo delta-4-steroids / 17-hydroxysteroids / 11-oxosteroids / Delta-4-steroids / Cyclohexenones / Alpha-acyloxy ketones / Tertiary alcohols / Alpha-hydroxy ketones / Cyclic alcohols and derivatives
show 4 more
Substituents
Progestogin-skeleton / 20-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / Hydroxysteroid / 17-hydroxysteroid / 11-oxosteroid / Oxosteroid / Delta-4-steroid / Cyclohexenone
show 16 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
corticosteroid hormone (CHEBI:3897) / C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C08173) / C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030120)

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. Grossman R, Yehuda R, Golier J, McEwen B, Harvey P, Maria NS: Cognitive effects of intravenous hydrocortisone in subjects with PTSD and healthy control subjects. Ann N Y Acad Sci. 2006 Jul;1071:410-21. [PubMed:16891588]
  2. Rautanen A, Eriksson JG, Kere J, Andersson S, Osmond C, Tienari P, Sairanen H, Barker DJ, Phillips DI, Forsen T, Kajantie E: Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene. J Clin Endocrinol Metab. 2006 Nov;91(11):4544-51. Epub 2006 Aug 8. [PubMed:16895953]
  3. Hammer F, Stewart PM: Cortisol metabolism in hypertension. Best Pract Res Clin Endocrinol Metab. 2006 Sep;20(3):337-53. [PubMed:16980198]
  4. Shaw JR, Gabor K, Hand E, Lankowski A, Durant L, Thibodeau R, Stanton CR, Barnaby R, Coutermarsh B, Karlson KH, Sato JD, Hamilton JW, Stanton BA: Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic. Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R1052-60. Epub 2006 Oct 12. [PubMed:17038445]
  5. Sher L: Combined dexamethasone suppression-corticotropin-releasing hormone stimulation test in studies of depression, alcoholism, and suicidal behavior. ScientificWorldJournal. 2006 Oct 31;6:1398-404. [PubMed:17086345]
  6. Schlechte JA, Ginsberg BH, Sherman BM: Regulation of the glucocorticoid receptor in human lymphocytes. J Steroid Biochem. 1982 Jan;16(1):69-74. [PubMed:7062741]
  7. Schlechte JA, Sherman BM: Decreased glucocorticoid receptor binding in adrenal insufficiency. J Clin Endocrinol Metab. 1982 Jan;54(1):145-9. [PubMed:7054210]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [PubMed:10490933]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Drug created on July 06, 2007 14:32 / Updated on December 14, 2018 05:36