CORTISONE

US Previously Marketed

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H28O5
Molecular Weight	360.444
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)CC(=O)[C@@]3([H])[C@@]2([H])CCC4=CC(=O)CC[C@]34C

InChI

InChIKey=MFYSYFVPBJMHGN-ZPOLXVRWSA-N

InChI=1S/C21H28O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-15,18,22,26H,3-8,10-11H2,1-2H3/t14-,15-,18+,19-,20-,21-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/009866s98_105lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.wikidoc.org/index.php/Cortisone | https://www.drugs.com/pro/cortisone-acetate.html | https://www.ncbi.nlm.nih.gov/pubmed/2811372 | https://www.ncbi.nlm.nih.gov/pubmed/7358829 | https://books.google.com/books?id=Q1voCAAAQBAJ&pg=PA113&lpg=PA113&dq=CORTISONE+SULFATE&source=bl&ots=-bwZTb4Fzh&sig=4gjBk9MhoF8OrL-7I5c06Fr32A8&hl=en&sa=X&ved=0ahUKEwiblMuT9pfVAhXK4SYKHXKKB6wQ6AEITTAG#v=onepage&q=CORTISONE%20SULFATE&f=false | http://www.google.com.pg/patents/US20120135924 | http://www.google.com.pg/patents/US20120128785 | https://www.google.com/patents/US4450151

Cortisone is a hormone that is FDA approved for the treatment of primary and secondary adrenocortical deficiency, rheumatic disorders, psoriasis, exfoliative dermatitis, bronchial asthma, allergic conjunctivitis, hemolytic anemia, enteritis, tuberculosis, trichnosis. 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. Common adverse reactions include convulsions, increased intracranial pressure with papilledema, vertigo, headache, psychic disturbances, hirsuitism, glaucoma, exophthalmos. Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression. Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Cortisone is a natural steroid hormone. Its sulfate analog has been detected in in umbilical vein blood fetus plasma between 19 and 32 weeks of gestation with a significant increase at 29-30 weeks and in amniotic fluid. Base on the experiments with rats it was suggested that cortisone sulfate in mammals could be hydrolyzed enzymatically liberating sulfate ions from cortisone. Cortisone sulfate has been proposed for use as one of the glycosaminoglycan compound materials in a cartilage prosthesis and biological nasal bridge implant manufacture as well as auxiliary agent in powder aerosol composition for use in baby powder, dry shampoo, water-eczema remedy and antiperspirant.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glucocorticoid receptor 172 Target ID: CHEMBL2034 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15705660	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Severe or incapacitating allergic conditions 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/009866s98_105lbl.pdf	Primary	Approved 8429	SOLU-CORTEF Approved Use Treatment of the Allergic states, Dermatologic diseases, Endocrine disorders, Gastrointestinal diseases, Hematologic disorders, Neoplastic diseases, Rheumatic disorders, Respiratory diseases, Renal diseases, Ophthalmic diseases, Nervous System Launch Date 1955
Rheumatic diseases 30 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/009866s98_105lbl.pdf	Primary	Approved 8429	SOLU-CORTEF Approved Use Treatment of the Allergic states, Dermatologic diseases, Endocrine disorders, Gastrointestinal diseases, Hematologic disorders, Neoplastic diseases, Rheumatic disorders, Respiratory diseases, Renal diseases, Ophthalmic diseases, Nervous System. Launch Date 1955
Primary adrenocortical insufficiency 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/009866s98_105lbl.pdf	Primary	Approved 8429	SOLU-CORTEF Approved Use When oral therapy is not feasible, and the strength, dosage form, and route of administration of the drug reasonably lend the preparation to the treatment of the condition, the intravenous or intramusculat use of SOLU-CORTEF Sterile Powder is indicated as follows: Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice). Launch Date 1955

C_max

Value	Dose	Co-administered	Analyte	Population
477 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8284505	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		CORTISONE plasma	Canis lupus population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
1211 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8284505	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		CORTISONE plasma	Canis lupus population: HEALTHY age: ADULT sex: MALE food status: FASTED
4109 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6691888	44.8 mg 1 times / day steady-state, oral dose: 44.8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CORTISONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
23 min EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8284505	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		CORTISONE plasma	Canis lupus population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
16.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7195404/			CORTISONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:16962	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:16962
ChemicalBook	CB6413305	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6413305
MolPort	MolPort-002-529-087	https://www.molport.com/shop/molecule-link/MolPort-002-529-087
ZINC	ZINC000004083557	http://zinc15.docking.org/substances/ZINC000004083557
eMolecules	29503844	https://www.emolecules.com/cgi-bin/more?vid=29503844
eMolecules	493549	https://www.emolecules.com/cgi-bin/more?vid=493549

PubMed

Title	Date	PubMed
The excretion of free cortisol, cortisone, cortisol sulfate and cortisone sulfate in peripheral vascular disease, diabetes mellitus and hyperthyroidism.	1978 Nov	744572
Urinary free cortisol, cortisone, cortisol sulfate, cortisone sulfate and 17-ketosteroids in breast cancer.	1979	157439
Origin of corticosteroids in amniotic fluid.	1980 Mar	7358829
Corticosteroid sulfates in fetus plasma.	1989 Oct	2811372
Innate immunity and the normal microflora.	2000 Feb	10719663
Chemotherapy-related hemolytic-uremic syndrome following treatment of a carcinoma of the nasopharynx.	2001	11528253
Adrenocortical response and cortisone replacement in systemic inflammatory response syndrome.	2001 Apr	11314835
Cervical intramedullar schistosomiasis as a rare cause of acute tetraparesis.	2001 Apr	11311476
Apparent mineralocorticoid excess.	2001 Apr	11306334
Light and electron microscopy localization of the 11beta-hydroxysteroid dehydrogenase type I enzyme in the rat.	2001 Apr	11250946
[Idiopathic thrombocytopenia during pregnancy. The risk in connection with umbilical blood sampling is probably greater than the benefit].	2001 Aug 8	11526659
Increased ACTH levels do not alter renal 11beta-hydroxysteroid dehydrogenase type 2 gene expression in the sheep.	2001 Feb	11403098
[Serious life events and congenital malformations. A national study with a complete follow-up].	2001 Feb 19	11242661
A population physiologically based pharmacokinetic/pharmacodynamic model for the inhibition of 11-beta-hydroxysteroid dehydrogenase activity by glycyrrhetic acid.	2001 Jan 1	11141355
Induction of p53 expression in skin by radiotherapy and UV radiation: a randomized study.	2001 Jan 17	11208882
Serum cortisol/cortisone ratio after Synacthen stimulation.	2001 Jul	11522281
Effects of growth hormone replacement on cortisol metabolism in hypopituitary patients treated with cortisone acetate.	2001 Jul	11465341
Glucocorticoid induction of the glaucoma gene MYOC in human and monkey trabecular meshwork cells and tissues.	2001 Jul	11431441
The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2.	2001 Jul 27	11350956
Outpatient laparoscopic adrenalectomy in patients with Conn's syndrome.	2001 Jun	11591947
Activation of the hypothalamic-pituitary-adrenal axis in obesity: cause or consequence?	2001 Jun	11527096
Effect of naloxone therapy on depersonalization: a pilot study.	2001 Jun	11448093
Short term respiratory effects of acute exposure to chlorine due to a swimming pool accident.	2001 Jun	11351056
Functional expression, characterization, and purification of the catalytic domain of human 11-beta -hydroxysteroid dehydrogenase type 1.	2001 Jun 15	11294832
Decreased gene expression of 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase in human placenta of patients with preeclampsia.	2001 Mar	11238526
Sarcoidosis: old and new treatments.	2001 May	11312398
Hydrolysis of conjugated steroids by the combined use of beta-glucuronidase preparations from helix pomatia and ampullaria: determination of urinary cortisol and its metabolites.	2001 Nov	11576618
Glucocorticoid metabolism and adrenocortical reactivity to ACTH in myotonic dystrophy.	2001 Sep	11549662
[Chronic respiratory failure and osteoporosis: a difficult problem to unravel].	2001 Sep	11547239
Intraocular injection of crystalline cortisone as adjunctive treatment of diabetic macular edema.	2001 Sep	11530068

Patents

Sample Use Guides

In Vivo Use Guide

Therapy is initiated by administering hydrocortisone sterile powder intravenously over a period of 30 seconds (e.g., 100 mg) to 10 minutes (e.g., 500 mg or more). In general, high dose corticosteroid therapy should be continued only until the patient’s condition has stabilized, usually not beyond 48 to 72 hours.

Route of Administration: Other

In Vitro Use Guide

With the highest concentration of cortisone that can be used under these conditions (owing to the limitation of solubility), namely 10 ug/ml., it is only possible to kill about 50 % of the lymphocytes in 46 hr; and, by extrapolation of the curve, that a concentration of about 10 mg/ml. would be required to kill 99 % of them.

Name

Type

Language

CORTISONE

Official Name

English

CORTISONE [USP-RS]

Common Name

English

17,21-DIHYDROXYPREGN-4-ENE-3,11,20-TRIONE

Systematic Name

English

Cortisone [WHO-DD]

Common Name

English

PREGN-4-ENE-3,11,20-TRIONE, 17,21-DIHYDROXY-

Systematic Name

English

cortisone [INN]

Common Name

English

PREDNISONE IMPURITY A [EP IMPURITY]

Common Name

English

NSC-9703

Code

English

HYDROCORTISONE IMPURITY B [EP IMPURITY]

Common Name

English

CORTISONE [MI]

Common Name

English

CORTISONE [VANDF]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175576