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Hydrocortisone

PubChem CID
5754
Structure
Hydrocortisone_small.png
Hydrocortisone_3D_Structure.png
Hydrocortisone__Crystal_Structure.png
Molecular Formula
Synonyms
  • hydrocortisone
  • Cortisol
  • 50-23-7
  • Acticort
  • Cetacort
Molecular Weight
362.5 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
Cortisol is a 17alpha-hydroxy-C21-steroid that is pregn-4-ene substituted by oxo groups at positions 3 and 20 and hydroxy groups at positions 11, 17 and 21. Cortisol is a corticosteroid hormone or glucocorticoid produced by zona fasciculata of the adrenal cortex, which is a part of the adrenal gland. It is usually referred to as the "stress hormone" as it is involved in response to stress and anxiety, controlled by corticotropin-releasing hormone (CRH). It increases blood pressure and blood sugar, and reduces immune responses. It has a role as an anti-inflammatory drug, an anti-allergic agent, an anti-asthmatic drug, a human metabolite, a mouse metabolite and a drug allergen. It is a 21-hydroxy steroid, an 11beta-hydroxy steroid, a 20-oxo steroid, a 3-oxo-Delta(4) steroid, a primary alpha-hydroxy ketone, a tertiary alpha-hydroxy ketone, a 17alpha-hydroxy-C21-steroid and a glucocorticoid. It derives from a hydride of a pregnane.
Hydrocortisone, or cortisol, is a glucocorticoid secreted by the adrenal cortex. Hydrocortisone is used to treat immune, inflammatory, and neoplastic conditions. It was discovered in the 1930s by Edward Kendall and named Compound F, or 17-hydroxycorticosterone. Hydrocortisone was granted FDA approval on 5 August 1952.
Hydrocortisone is a Corticosteroid. The mechanism of action of hydrocortisone is as a Corticosteroid Hormone Receptor Agonist.
See also: Acetic acid, glacial; hydrocortisone (annotation moved to); Hydrocortisone Acetate (annotation moved to); Hydrocortisone; polymyxin B sulfate (annotation moved to) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Hydrocortisone.png

1.2 3D Conformer

1.3 Crystal Structures

1 of 4
View All
CCDC Number
Associated Article
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C21H30O5/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/h9,14-16,18,22,24,26H,3-8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

JYGXADMDTFJGBT-VWUMJDOOSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2[C@H](C[C@]4([C@H]3CC[C@@]4(C(=O)CO)O)C)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C21H30O5
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

50-23-7

2.3.2 Deprecated CAS

1050676-88-4, 1436392-18-5, 8056-08-4, 80562-38-5, 8063-42-1
1050676-88-4, 80562-38-5, 8063-42-1

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 HMDB ID

2.3.10 KEGG ID

2.3.11 Lipid Maps ID (LM_ID)

2.3.12 Metabolomics Workbench ID

2.3.13 NCI Thesaurus Code

2.3.14 Nikkaji Number

2.3.15 NSC Number

2.3.16 PharmGKB ID

2.3.17 Pharos Ligand ID

2.3.18 RXCUI

2.3.19 Wikidata

2.3.20 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 11 Epicortisol
  • 11-Epicortisol
  • Cortef
  • Cortifair
  • Cortisol
  • Cortril
  • Epicortisol
  • Hydrocortisone
  • Hydrocortisone, (11 alpha)-Isomer
  • Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer
  • Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
362.5 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
1.6
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
362.20932405 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
362.20932405 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
94.8 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
26
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
684
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
7
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Solid

3.2.2 Color / Form

Plates from alc or iso-propyl alc
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V5: 4244
Crystalline, striated blocks from absolute ethanol or isopropanol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 855
White, crystalline powder
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 585

3.2.3 Odor

Odorless
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 585

3.2.4 Taste

Bitter taste
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 585

3.2.5 Melting Point

220 °C
PhysProp
217-220 °C with some decomposition
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 855
220 °C

3.2.6 Solubility

320 mg/L (at 25 °C)
YALKOWSKY,SH & DANNENFELSER,RM (1992)
Amorphous, hygroscopic, white powder. Mp 169.0-171.2 °C. Solubility in water: approx 500 mg/mL. Similarly soluble in methanol, ethanol,; sparingly soluble in chloroform. /21-Sodium succinate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 855
Solubilities in various solvents
Solvent
Ethanol
mg/mL at 25 °C
15.0
Solvent
Methanol
mg/mL at 25 °C
6.2
Solvent
Acetone
mg/mL at 25 °C
9.3
Solvent
Chloroform
mg/mL at 25 °C
1.6
Solvent
Ether
mg/mL at 25 °C
0.35
Solvent
Propylene glycol
mg/mL at 25 °C
12.7
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 855
Soluble in concentrated sulfuric acid with intense green flourescence
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 855
Soluble in dioxane
Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 3-286
In water, 320 mg/L at 25 °C
Yalkowsky, S.H., He, Yan., Handbook of Aqueous Solubility Data: An Extensive Compilation of Aqueous Solubility Data for Organic Compounds Extracted from the AQUASOL dATAbASE. CRC Press LLC, Boca Raton, FL. 2003., p. 1183
0.32 mg/mL

3.2.7 LogP

1.61
HANSCH,C ET AL. (1995)
log Kow = 1.61
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 174
1.61
HANSCH,C ET AL. (1995)

3.2.8 LogS

-2.97
ADME Research, USCD

3.2.9 Stability / Shelf Life

SENSITIVE TO LIGHT
Hawley, G.G. The Condensed Chemical Dictionary. 9th ed. New York: Van Nostrand Reinhold Co., 1977., p. 449
VERY STABLE @ ROOM TEMP EXCEPT IN PRESENCE OF ALKALIS OR STRONG ACIDS
Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 265

3.2.10 Optical Rotation

Specific optical rotation: +167 deg at 22 °C/D (absolute alc)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V5: 4244

3.2.11 Caco2 Permeability

-4.66
ADME Research, USCD

3.2.12 Collision Cross Section

185.1 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

212.9 Ų [M+Na]+ [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

210.7 Ų [M+K]+ [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

191.9 Ų [M-H]- [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

188.6 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

189.27 Ų [M+H]+ [CCS Type: DT; Method: stepped-field]

213.72 Ų [M+Na]+ [CCS Type: DT; Method: stepped-field]

186.6 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

184.11 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

180.18 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111

182.99 Ų [M-H2O-H]- [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

189.1 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

213.91 Ų [M+Na]+ [CCS Type: DT; Method: stepped-field]

188.88 Ų [M+H]+ [CCS Type: DT; Method: stepped-field]

192.1 Ų [M-H]-

188.9 Ų [M+H]+

213.2 Ų [M+K]+

211.6 Ų [M+Na]+

S50 | CCSCOMPEND | The Unified Collision Cross Section (CCS) Compendium | DOI:10.5281/zenodo.2658162

188.95 Ų [M+Cl]-

191.54 Ų [M+HCOO]-

187.79 Ų [M+H]+

191.98 Ų [M-H]-

S61 | UJICCSLIB | Collision Cross Section (CCS) Library from UJI | DOI:10.5281/zenodo.3549476

3.2.13 Other Experimental Properties

COMMERCIAL SAMPLES: MP 212-213 °C. SPECIFIC OPTICAL ROTATION: +163 DEG @ 22 °C/D (METHANOL, 0.5%)
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 630
Monoclinic, sphenoidal, tabular crystals from dilute acetone. Tasteless. Specific gravity: 1.289 at 20 °C/4 °C; decomposes at 223 °C. Specific optical rotation: +166 deg ( c = 0.4 in dioxane); +155.7 deg ( C = 0.5 in acetone). UV max (methanol): 242 nm (E = 390, 1%, 1 cm). Somewhat hygroscopic. Solubility in water: 1 mg/100 mL; in ethanol: 0.45 g/100 mL; in methanol: 3.9 mg/mL; in acetone: 1.1 mg/g; in ether: 0.15 mg/mL. One gram dissolves in about 200 mL chloroform. Very soluble in DMF; soluble in dioxane. /21-Acetate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 855
UV: 1893 (Absorption Spectra in the UV and visible Regions, Academic Press, New York) /Hydrocortisone, acetate/
Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V1 751
Mol wt: 486.40. White powder. UV max (methanol): 242 nm (A=298-341, 1%, 1cm). Specific optical rotation: +120 °C/D (water). Solubility in water (25 °C): >500 mg/mL. pH of a 1% aqueous solution: 7.5-8.5 /21-Phosphate disodium salt/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 855
Mol wt: 432.55 /17-Butyrate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 855
Mol wt: 446.57 /17-Valerate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 855
MP: 168-169 °C & 229-230 °C; SPECIFIC OPTICAL ROTATION: +152 DEG @ 25 °C/D (CHLOROFORM); MAX ABSORPTION (METHANOL): 242 NM (E= 372, 1%, 1 CM) /TEBUTATE/
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 630
ODORLESS /HYDROCORTISONE & SALTS/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 893
PH: 7.5-8.5 (1% SOLN) /SODIUM PHOSPHATE/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 893
SPECIFIC OPTICAL ROTATION: +142 TO +152 DEG /CYPIONATE/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 893

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Pharmaceutical

3.4.1 Drugs

Pharmaceuticals -> Steroids
S56 | UOATARGPHARMA | Target Pharmaceutical/Drug List from University of Athens | DOI:10.5281/zenodo.3248837
S57 | GREEKPHARMA | Suspect Pharmaceuticals from the National Organization of Medicine, Greece | DOI:10.5281/zenodo.3248883
Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.4.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Corticosteroids, Systemic; Glucocorticoids; Anti-Inflammatory Agents
Breast Feeding; Lactation; Milk, Human; Corticosteroids, Topical; Glucocorticoids; Anti-Inflammatory Agents
Human drug -> Discontinued
Human drug -> Prescription; Discontinued
Human drug -> Prescription
Human drug -> Prescription; Discontinued; Active ingredient (HYDROCORTISONE)
Human drugs -> Corticosteroids for systemic use -> Human pharmacotherapeutic group -> EMA Drug Category
Paediatric drug

Adrenal hormones and synthetic substitutes

Anti-inflammatory medicines

Antiallergics and medicines used in anaphylaxis

Dermatological medicines > Anti-inflammatory and antipruritic medicines

Hormones and antihormones

Ophthalmological preparations > Anti-inflammatory agents

3.4.1.2 Animal Drugs
Active Ingredients (Hydrocortisone) -> FDA Greenbook
Pharmaceuticals -> Animal Drugs -> Approved in Taiwan
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

3.4.2 Endocrine Disruptors

Potential endocrine disrupting compound
S109 | PARCEDC | List of 7074 potential endocrine disrupting compounds (EDCs) by PARC T4.2 | DOI:10.5281/zenodo.10944198

3.4.3 Lipids

Lipids -> Sterol Lipids [ST] -> Steroids [ST02] -> C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives [ST0203]

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 1H NMR Spectra

Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
286095
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 2
Source of Sample
E. Merck AG, Darmstadt, Germany
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 9
View All
Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

103.0 1

91.0 0.64

84.0 0.63

89.0 0.61

105.0 0.47

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2 of 9
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Spectra ID
Instrument Type
GC-EI-TOF
Ionization Mode
positive
Top 5 Peaks

91.0 100

105.0 47.65

93.0 41.34

152.0 34.23

117.0 28.43

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Notes
instrument=Leco Pegasus IV

4.2.2 MS-MS

1 of 9
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

363.2158 100

327.1947 33.42

364.2197 25.12

309.184 20.66

121.0639 18.26

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Spectra ID
Ionization Mode
Positive
Top 5 Peaks

121.064 100

259.1689 57.16

145.1 46.95

131.0842 43.84

143.0841 39.24

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4.2.3 LC-MS

1 of 93
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Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6560 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20 eV
Fragmentation Mode
CID
Column Name
Direct injection
Retention Time
0.180 min
Precursor m/z
363.2166
Precursor Adduct
[M+H]+
Top 5 Peaks

121.065 999

97.0646 333

363.2144 292

267.1743 262

309.1838 260

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License
CC BY
2 of 93
View All
Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6560 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Column Name
Direct injection
Retention Time
0.180 min
Precursor m/z
363.2166
Precursor Adduct
[M+H]+
Top 5 Peaks

363.2167 999

121.0646 312

309.185 164

327.1937 137

345.2049 128

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License
CC BY

4.2.4 Other MS

1 of 2
Other MS
MASS: 62042 (NIST/EPA/MSDC Mass Spectral Database, 1990 version)
2 of 2
Authors
YAMAMOTO M, DEP. CHEMISTRY, FAC. SCIENCE, NARA WOMEN'S UNIV.
Instrument
HITACHI M-2500
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ENERGY 70 eV
Top 5 Peaks

332 999

362 677

302 632

163 608

344 571

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License
CC BY-NC-SA

4.3 UV Spectra

Max absorption: 242 nm (e= 445, 1%, 1 cm)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 855
ABSORPTIVITY OF SOLN IN METHANOL (1 IN 1000,000) @ 242 NM DOES NOT DIFFER BY MORE THAN 2.5%
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 893
UV: 20770 (Sadtler Research Laboratories Spectral Collection)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V5: 4244

4.4 IR Spectra

IR Spectra
IR: 5234 (Coblentz Society Spectral Collection)

4.4.1 FTIR Spectra

1 of 2
Technique
KBr WAFER
Source of Sample
E. MERCK AG, DARMSTADT, GERMANY
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
Mull
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Aldrich
Catalog Number
286095
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4.2 ATR-IR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids Inc.
Catalog Number
Q3880-000
Lot Number
B0948
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Sample
Aldrich
Catalog Number
286095
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 Raman Spectra

Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids Inc.
Catalog Number
Q3880-000
Lot Number
B0948
Copyright
Copyright © 2013-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.6 Other Spectra

SADTLER REFERENCE NUMBER: 8758 (IR, PRISM)
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-255

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Otic solutions are indicated for infections of the external auditory canal caused by susceptible organisms and with inflammation. Hydrocortisone tablets are indicated for certain endocrine, rheumatic, collagen, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, gastrointestinal, and other conditions. A hydrocortisone enema is indicated for ulcerative colitis, a topical ointment with antibiotics is indicated for corticosteroid responsive dermatoses with infections, and a topical cream with [acyclovir] is indicated to treat cold sores. Oral granules of hydrocortisone are used as a replacement therapy for Adrenocortical Insufficiency (AI) in children under 17 years of age.
Treatment of adrenal insufficiency in adults.

7.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Corticosteroids, Systemic; Glucocorticoids; Anti-Inflammatory Agents
Breast Feeding; Lactation; Milk, Human; Corticosteroids, Topical; Glucocorticoids; Anti-Inflammatory Agents

7.3 Drug Transformations

Hydrocortisone has known transformation products that include Cortisone.
S66 | EAWAGTPS | Parent-Transformation Product Pairs from Eawag | DOI:10.5281/zenodo.3754448

7.4 FDA Medication Guides

Drug
Active Ingredient
Hydrocortisone
Form;Route
GRANULE;ORAL
Company
ETON
Date
06/05/2024

7.5 WHO Essential Medicines

Drug
Drug Classes
Adrenal hormones and synthetic substitutes
Formulation
Oral - Solid: 5 mg; 10 mg; 20 mg
Indication
Adrenocortical insufficiency
Drug
Drug Classes
Anti-inflammatory medicines
Formulation
(1) Local - Rectal - Suppository: 25 mg (acetate); (2) Local - Rectal - Retention enema: 100 mg per 60 mL
Indication
(1) Crohn disease site; (2) Ulcerative colitis
Drug
Drug Classes
Antiallergics and medicines used in anaphylaxis
Formulation
Parenteral - General injections - unspecified: 100 mg in vial powder for injection (as sodium succinate)
Indication
Anaphylaxis
Drug
Drug Classes
Dermatological medicines > Anti-inflammatory and antipruritic medicines
Formulation
(1) Local - Topical - Cream: 1% (acetate); (2) Local - Topical - Ointment: 1% (acetate)
Indication
(1) Dermatitis or eczema; (2) Lichen planus; (3) Pruritus due to skin disorder; (4) Psoriasis of unspecified type
Drug
Drug Classes
Hormones and antihormones
Formulation
Parenteral - General injections - unspecified: 100 mg in vial (as sodium succinate)
Indication
(1) Lymphoid leukaemia, not elsewhere classified; (2) Unspecified malignant neoplasms of ill-defined or unspecified sites; (3) Burkitt lymphoma including Burkitt leukaemia
Drug
Drug Classes
Ophthalmological preparations > Anti-inflammatory agents
Formulation
Local - Ophthalmological - Ointment: 1% (acetate)
Indication
(1) Scleritis; (2) Anterior uveitis

7.6 FDA Approved Drugs

7.7 FDA Orange Book

7.8 FDA National Drug Code Directory

7.9 FDA Green Book

7.10 Drug Labels

Homeopathic product and label
Drug and label
Active ingredient and drug
Homeopathic product and label

7.11 Clinical Trials

7.11.1 ClinicalTrials.gov

7.11.2 EU Clinical Trials Register

7.11.3 NIPH Clinical Trials Search of Japan

7.12 EMA Drug Information

1 of 4
View All
Medicine
Category
Human drugs
Therapeutic area
Adrenal Insufficiency
Active Substance
hydrocortisone
INN/Common name
hydrocortisone
Pharmacotherapeutic Classes
Corticosteroids for systemic use
Status
This medicine is authorized for use in the European Union
Company
Takeda Pharmaceuticals International AG Ireland Branch
Market Date
2011-11-03
2 of 4
View All
Medicine
Category
Human drugs
Therapeutic area
Adrenal Hyperplasia, Congenital
Active Substance
hydrocortisone
INN/Common name
hydrocortisone
Pharmacotherapeutic Classes
Corticosteroids for systemic use
Status
This medicine is authorized for use in the European Union
Company
Diurnal Europe B.V.
Market Date
2021-05-27

7.13 Therapeutic Uses

Anti-Inflammatory Agents, Steroidal
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
MEDICATION (VET): Acute urticaria /can be treated by/ rapid-acting adrenocorticosteroids, eg, hydrocortisone ... .
Kahn, C.M. (Ed.); The Merck Veterinary Manual 9th ed. Merck & Co. Whitehouse Station, NJ. 2005, p. 690
MEDICATION (VET): /USED/ IV, IN PREVENTING OR TREATING ADRENAL FAILURE & SHOCK-LIKE CONDITIONS IN SURGICAL CASES WHICH HAVE BEEN ON CORTICOSTEROIDS, IN ACUTE ALLERGIC REACTIONS...IN POOR SURGICAL RISKS, & IN CASES WHICH HAVE HAD OVERWHELMING SYSTEMIC INFECTIONS...IN DOGS OR CATTLE...
Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 266
MEDICATION (VET) /EXPL:/: 5 Standardbreds and 4 Dutch Warmblood horses /were/ used to examine sensitivity of peripheral tissues to exogenous insulin 24 hours after administration of a single dose of hydrocortisone (0.06 mg/kg), eGH (20 ug/kg), or saline (0.9% NaCl) solution and after long-term administration (11 to 15 days) of eGH to horses. The amounts of metabolized glucose (M) and plasma insulin concentration (I) were determined. Values for M and the M-to-I ratio were significantly higher 24 hours after administration of a single dose of hydrocortisone than after single-dose administration of eGH or saline solution. After long-term administration of eGH, basal I concentration was increased and the mean M-to-I ratio was 22% lower, compared with values for horses treated with saline solution. Increases in M and the M-to-I ratio after a single dose of hydrocortisone imply that short-term hydrocortisone treatment increases glucose use by, and insulin sensitivity of, peripheral tissues. Assuming a single dose of hydrocortisone improves sensitivity of peripheral tissues to insulin, it may be an interesting candidate for use in reducing insulin resistance in peripheral tissues of horses with several disease states.
de Graaf-Roelfsema E et al; Am J Vet Res 66 (11): 1907-13 (2005)
For more Therapeutic Uses (Complete) data for HYDROCORTISONE (23 total), please visit the HSDB record page.

7.14 Drug Warnings

It is not known whether rectal corticosteroids are distributed into breast milk. Systemic corticosteroids are distributed into breast milk and may cause unwanted effects, such as growth suppression, in the infant. Rectal corticosteroids are not recommended for use by breast-feeding mothers. /Corticosteroids, rectal/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 913
The results of a prospective randomized controlled trial, which looked at the incidence of postoperative diabetes insipidus following the use of three different hydrocortisone protocols, and the results of a study, on the incidence of diabetes insipidus and cortisol response in patients not given hydrocortisone /was reported/. In study 1, 114 patients with pituitary macroadenoma were randomized into three groups: conventional dose (injected hydrocortisone 100 mg IV 6-hourly for 3 days); intermediate dose (injected hydrocortisone 100 mg IV 6-hourly on day 1, 100 mg IV 8-hourly on day 2, and 100 mg IV 12-hourly on day 3); low dose protocol (injected hydrocortisone 25 mg IV 6-hourly on day 1, 25 mg IV 8-hourly on day 2 and 25 mg IV 12-hourly on day 3). Radical excision was achieved in 92 patients. The incidence of diabetes insipidus with the conventional dose was 52%, intermediate dose, 36% and low dose, 24% (p = 0.025). Study 2 included 16 consecutive patients with Hardy's grade A & B pituitary adenoma. These patients were randomized to receive (Group I) or not receive (Group II) hydrocortisone. Patients in Group II demonstrated normal cortisol response intraoperatively and no patient developed features of hypocortisolism; the incidence of diabetes insipidus in this group was 14%. The low dose hydrocortisone protocol reduced the incidence of diabetes insipidus by 46% when compared with the conventional dose hydrocortisone protocol. In patients with grade A and B tumor with normal preoperative cortisol levels, the use of perioperative hydrocortisone can be avoided.
Rajaratnam S et al; Br J Neurosurg 17 (5): 437-42 (2003)
ACUTE ADRENAL INSUFFICIENCY RESULTS FROM TOO RAPID WITHDRAWAL OF CORTICOSTEROID THERAPY. /CORTICOSTEROIDS/
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1496
POTENTIAL ADVERSE EFFECTS ON FETUS: Cleft palate, spontaneous abortions, and intrauterine growth retardation in animals. Potential for cleft palate formation and adrenal suppression in humans, although teratogenic effects have not been confirmed. POTENTIAL SIDE EFFECTS ON BREAST-FED INFANT: Passes into breast milk in small amounts. Administration of physiologic doses unlikely to adversely affect infant. FDA Category: C (C = Studies in laboratory animals have revealed adverse effects on the fetus (teratogenic, embryocidal, etc.) but there are no controlled studies in pregnant women. The benefits from use of the drug in pregnant women may be acceptable despite its potential risks, or there are no laboratory animal studies or adequate studies in pregnant women.) /Adrenocorticosteroids/ /from table II/
Stockton DL, Palle AS; J Am Acad Dermatol 23 (1): 87-103 (1990)
For more Drug Warnings (Complete) data for HYDROCORTISONE (31 total), please visit the HSDB record page.

7.15 Biomarker Information

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Hydrocortisone binds to the glucocorticoid receptor leading to downstream effects such as inhibition of phospholipase A2, NF-kappa B, other inflammatory transcription factors, and the promotion of anti-inflammatory genes. Hydrocortisone has a wide therapeutic index and a moderate duration of action. Patients should stop taking the medication if irritation or sensitization occurs.

8.2 MeSH Pharmacological Classification

Anti-Inflammatory Agents
Substances that reduce or suppress INFLAMMATION. (See all compounds classified as Anti-Inflammatory Agents.)

8.3 FDA Pharmacological Classification

1 of 2
FDA UNII
WI4X0X7BPJ
Active Moiety
HYDROCORTISONE
Pharmacological Classes
Established Pharmacologic Class [EPC] - Corticosteroid
Pharmacological Classes
Mechanisms of Action [MoA] - Corticosteroid Hormone Receptor Agonists
FDA Pharmacology Summary
Hydrocortisone is a Corticosteroid. The mechanism of action of hydrocortisone is as a Corticosteroid Hormone Receptor Agonist.
2 of 2
Non-Proprietary Name
HYDROCORTISONE
Pharmacological Classes
Corticosteroid [EPC]; Corticosteroid Hormone Receptor Agonists [MoA]

8.4 ATC Code

H02AB09
S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

D - Dermatologicals

D07 - Corticosteroids, dermatological preparations

D07X - Corticosteroids, other combinations

D07XA - Corticosteroids, weak, other combinations

D07XA01 - Hydrocortisone

S - Sensory organs

S01 - Ophthalmologicals

S01B - Antiinflammatory agents

S01BA - Corticosteroids, plain

S01BA02 - Hydrocortisone

S - Sensory organs

S02 - Otologicals

S02B - Corticosteroids

S02BA - Corticosteroids

S02BA01 - Hydrocortisone

S - Sensory organs

S01 - Ophthalmologicals

S01C - Antiinflammatory agents and antiinfectives in combination

S01CB - Corticosteroids/antiinfectives/mydriatics in combination

S01CB03 - Hydrocortisone

A - Alimentary tract and metabolism

A01 - Stomatological preparations

A01A - Stomatological preparations

A01AC - Corticosteroids for local oral treatment

A01AC03 - Hydrocortisone

C - Cardiovascular system

C05 - Vasoprotectives

C05A - Agents for treatment of hemorrhoids and anal fissures for topical use

C05AA - Corticosteroids

C05AA01 - Hydrocortisone

D - Dermatologicals

D07 - Corticosteroids, dermatological preparations

D07A - Corticosteroids, plain

D07AA - Corticosteroids, weak (group i)

D07AA02 - Hydrocortisone

H - Systemic hormonal preparations, excl. sex hormones and insulins

H02 - Corticosteroids for systemic use

H02A - Corticosteroids for systemic use, plain

H02AB - Glucocorticoids

H02AB09 - Hydrocortisone

A - Alimentary tract and metabolism

A07 - Antidiarrheals, intestinal antiinflammatory/antiinfective agents

A07E - Intestinal antiinflammatory agents

A07EA - Corticosteroids acting locally

A07EA02 - Hydrocortisone

S01BA02; H02AB09; D07AA02; A07EA02

8.5 Absorption, Distribution and Excretion

Absorption
The pharmacokinetics of hydrocortisone can vary by 10 times from patient to patient. Following the oral administration of hydrocortisone at a dose of 0.2-0.3 mg/kg/day, the mean Cmax and AUC of plasma free cortisol were 32.69 nmol/L and 90.63 h x nmol/L, respectively. The mean Cmax and AUC of plasma total cortisol were 514.47 nmol/L and 1743.93 h x nmol/L, respectively. Following the dose of 0.4-0.6 mg/kg/day, the mean Cmax and AUC of plasma free cortisol were 70.81 nmol/L and 199.11 h x nmol/L. The mean Cmax and AUC of plasma total cortisol were 754.94 nmol/L and 2533.02 h x nmol/L, respectively. Topical hydrocortisone cream is 4-19% bioavailable with a Tmax of 24h. Hydrocortisone retention enemas have a bioavailability of 0.810 for slow absorbers and 0.502 for rapid absorbers. Slow absorbers take up hydrocortisone at a rate of 0.361±0.255/h while fast absorbers take up hydrocortisone at a rate of 1.05±0.255/h. A 20mg IV dose of hydrocortisone has an AUC of 1163±277ng\*h/mL.
Route of Elimination
Corticosteroids are eliminated predominantly in the urine. However, data regarding the exact proportion is not readily available.
Volume of Distribution
Total hydrocortisone has a volume of distribution of 39.82L, while the free fraction has a volume of distribution of 474.38L.
Clearance
Total hydrocortisone by the oral route has a mean clearance of 12.85L/h, while the free fraction has a mean clearance of 235.78L/h. A 20mg IV dose of hydrocortisone has a clearance of 18.2±4.2L/h.
Following percutaneous penetration of a topical corticosteroid, the drug that is systemically absorbed probably follows the metabolic pathways of systemically administered corticosteroids. Corticosteroids usually are metabolized in the liver and excreted by the kidneys. Some topical corticosteroids and their metabolites are excreted in bile. /Topical corticosteroids/
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525
Topical application of corticosteroids to the mucosa of the genitourinary or lower intestinal tract may result in substantial systemic absorption of the drugs. In healthy individuals, as much as 30-90% of rectally administered hydrocortisone as a retention enema may be absorbed. Greater amounts of hydrocortisone may be absorbed rectally if the intestinal mucosa is inflamed.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525
Following topical application of a corticosteroid to most areas of normal skin, only minimal amounts of the drug reach the dermis and subsequently the systemic circulation; however, absorption is markedly increased when the skin has lost its keratin layer and can be increased by inflammation and/or diseases of the epidermal barrier (e.g., psoriasis, eczema). The drugs are absorbed to a greater degree from the scrotum, axilla, eyelid, face, and scalp than from the forearm, knee, elbow, palm, and sole. Even after washing the area being treated, prolonged absorption of the corticosteroid occurs, possibly because the drug is retained in the stratum corneum. /Topical corticosteroids/
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525
Percutaneous penetration of corticosteroids varies among individual patients and can be increased by the use of occlusive dressings, by increasing the concentration of the corticosteroid, and by using different vehicles. The use of an occlusive dressing with hydrocortisone for 96 hours substantially enhances percutaneous penetration of the drug; however, such use for up to 24 hours does not appear to alter penetration of topically applied hydrocortisone.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525
For more Absorption, Distribution and Excretion (Complete) data for HYDROCORTISONE (15 total), please visit the HSDB record page.

8.6 Metabolism / Metabolites

Hydrocortisone is metabolised to 6-beta hydrocortisol via CYP3A, 5-beta tetrahydrocortisol via 3-oxo-5-beta-steroid 4-dehydrogenase, 5-alpha tetrahydrocortisol via 3-oxo-5-alpha-steroid 4-dehydrogenase 2, cortisone via Corticosteroid 11-beta-dehydrogenase isozyme 1 and Corticosteroid 11-beta-dehydrogenase isozyme 2, and glucuronide products. Cortisone is further metabolized to tetrahydrocortisone and dihydrocortisol.
A study was made of the absorption of exogenous hydrocortisone and formation of its metabolites in isolated liver of intact and exposed rats in conditions of recirculating perfusion. It was shown that the absorption of the hormone by the liver of irradiated rats was greatly lowered but the content of most metabolites found in the perfused medium of irradiated liver increased as compared to the control. It is suggested that irradiation inhibits subsequent transformations of the hydrocortisone metabolism products.
Litskevich LA, Dokshina GA; Radiobiologiia 25 (2): 200-3 (1985)
Subcellular distribution of (3)H-hydrocortisone and its metabolites in the liver and kidney of intact and alloxan diabetic rats was investigated. Ten minutes after the administration of this hormone several metabolites (mostly tetrahydrocortisol) and the native hormone were found in liver cytosol, microsomes, mitochondria and nuclei, the relative content of individual compounds in various subcellular fractions being different. In liver mitochondria, microsomes and nuclei of alloxan diabetic rats the concentration of tetrahydrocortisol was decreased, while that of native hormone was increased as compared to normal animals. It was suggested that such changes found in diabetic animals may be one of the causes of increased sensitivity of transcription and translation processes to glucocorticoids. In kidney cytosol and microsomes of intact rats cortisone and tetrahydrocortisol were found. In diabetic animals, however, the concentration of tetrahydrocortisol increased, while that of cortisone was undetectable.
Minchenko AG, Tronjko ND; Endocrinol Exp 22 (1): 19-28 (1988)

8.7 Biological Half-Life

Total hydrocortisone via the oral route has a half life of 2.15h while the free fraction has a half life of 1.39h. A 20mg IV dose of hydrocortisone has a terminal half life of 1.9±0.4h.
... After IV administration, hydrocortisone was eliminated with a total body clearance of 18 L/hr and a half-life of 1.7 hr.
Derendorf H et al; J Clin Pharmacol 31 (5): 473-6 (1991)

8.8 Mechanism of Action

The short-term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.
Following topical application, corticosteroids produce anti-inflammatory, antipruritic, and vasoconstrictor actions. The activity of the drugs is thought to result at least in part from binding with a steroid receptor. Corticosteroids decrease inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown. Corticosteroids, especially the fluorinated corticosteroids, have antimitotic activity on cutaneous fibroblasts and the epidermis. /Corticosteroids/
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525
Reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNL) and mononuclear cells (MNC) is inhibited following the intravenous administration of hydrocortisone. This is associated with a parallel decrease in intranuclear NFkappaB, known to modulate inflammatory responses including ROS generation. Plasma levels of interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine produced by TH2 cells, are also increased after hydrocortisone administration. In this study, we have investigated the effect of hydrocortisone on p47(phox) subunit, a key component of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, in MNC and the pharmacodynamics of this effect with ROS generation and plasma IL-10 levels /were investigated/. p47(phox) subunit protein levels in MNC showed a progressive decrease after hydrocortisone administration. It reached a nadir at 4 hours and increased thereafter to a baseline level at 24 hours. ROS generation also decreased, reached a nadir between 2 and 4 hours, and returned to a baseline level at 24 hours. IL-10 concentrations increased, peaked at 4 hours, and reverted to the baseline levels at 24 hours. In conclusion, p47(phox) subunit suppression may contribute to the inhibition of ROS generation in MNC after hydrocortisone administration. This suppression occurs in parallel with the suppression of NFkappaB and an increase in IL-10 plasma levels. Therefore, it would appear that the decrease in intranuclear NFkappaB and an increase in IL-10 may cause the inhibitory modulation on p47(phox) subunit and ROS generation by MNC following hydrocortisone and other glucocorticoids.
Dandona P et al; Metabolism 50 (5): 548-52 (2001)

8.9 Human Metabolite Information

8.9.1 Tissue Locations

  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Gland
  • Adrenal Medulla
  • Bladder
  • Brain
  • Epidermis
  • Fibroblasts
  • Intestine
  • Kidney
  • Leukocyte
  • Liver
  • Neuron
  • Ovary
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Testis

8.9.2 Cellular Locations

  • Cytoplasm
  • Endoplasmic reticulum
  • Extracellular
  • Membrane
  • Mitochondria

8.9.3 Metabolite Pathways

8.10 Biochemical Reactions

8.11 Transformations

9 Use and Manufacturing

9.1 Uses

EPA CPDat Chemical and Product Categories
The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products, Scientific Data, volume 5, Article number: 180125 (2018), DOI:10.1038/sdata.2018.125
Medicine (antiinflammatory agent), also used as the acetate and sodium succinate salts
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 585
THERAP CAT: Glucocorticoid
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 828
THERAP CAT (VET): Glucocorticoid
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 828
MEDICATION (VET)
MEDICATION

Use (kg; approx.) in Germany (2009): >1000

Use (kg) in USA (2002): 21000

Use (kg) in France (2004): 453

Consumption (g per capita; approx.) in Germany (2009): 0.0122

Consumption (g per capita) in the USA (2002): 0.0744

Consumption (g per capita) in France (2004): 0.0075

Excretion rate: 0.06

Calculated removal (%): 45.9

9.1.1 Use Classification

Human drugs -> Corticosteroids for systemic use -> Human pharmacotherapeutic group -> EMA Drug Category
Human Drugs -> EU pediatric investigation plans
Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Pharmaceuticals -> Animal Drugs -> Approved in Taiwan
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664
Pharmaceuticals -> Hormones -> Steroid hormones
S66 | EAWAGTPS | Parent-Transformation Product Pairs from Eawag | DOI:10.5281/zenodo.3754448

9.1.2 Household Products

Household & Commercial/Institutional Products

Information on 6 consumer products that contain Hydrocortisone in the following categories is provided:

• Personal Care

• Pet Care

9.2 Methods of Manufacturing

ISOLATION FROM ADRENAL GLANDS
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 828
Preparation by microbioal transformation: H.C. Murrary, D.H. Perterson, US 2602769 (1952 to Upjohn)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 828

9.3 Formulations / Preparations

Ointment: 0.5% Cortizone-5, (Pfizer), 1% Cortizone-10, (Pfizer), HydroSKIN, (Rugby), 2.5% Hytone, (Dermik). Pledgets (saturated with solution): 0.5% Massengill Medicated Soft Cloth Towelette (with parabens and propylene glycol), (GlaxoSmithKline). Solution: 1% Cortaid FastStick Maximum Strength (with alcohol and methylparaben), (Pfizer), Cortaid Spray Maximum Strength (with alcohol and methylparaben), (Pfizer), Cortizone-10 Scalp Itch Formula Liquid (with alcohol SD 40-2 60% v/v, benzyl alcohol, and propylene glycol), (Pfizer), Penecort (with alcohol SD 40-2 57%, benzyl alcohol, and propylene glycol), (Allergan), Texacort (with SD alcohol 33% and propylene glycol), (Sirius), 2.5% Texacort, (Sirius).
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3533
Lotion: 0.5% HydroSKIN, (Rugby). 1% Ala-Cort, (Del-Ray), Aquanil HC (with benzyl alcohol), (Person & Covey), Cetacort (with parabens), (Healthpoint), Dermacort (with benzyl alcohol), (Solvay) HydroSKIN, (Rugby) LactiCare-HC, (Stiefel) Nutracort (with parabens), (Healthpoint), Sarnol HC, (Stiefel), 2% Ala-Scalpt, (Del-Ray); 2.5% Hydrocortisone Lotion, (Glades), Hydrocortisone Lotion, (Major), Hytone (with propylene glycol), (Dermik), LactiCare-HC, (Stiefel), Nutracort (with parabens), (Healthpoint), ProctoCream-HC (with benzyl alcohol), (Physicians Total Care).
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3533
Topical: Cream: 0.5% Cortizone-5 (with aloe and parabens), (Pfizer), Cortizone for Kids ( with aloe and parabens), (Pfizer); 1% Ala-Cort, (Del-Ray), Cortaid Intensive Therapy (with parabens and propylene glycol), (Pfizer), Cortizone-10 (with aloe and parabens), (Pfizer), Cortizone-10 External Anal Itch Relief Creme ( with aloe and parabens), (Pfizer), Dermacort, (Solvay), DermiCort (Republic), HydroSKIN, (Rugby), Hytone (with propylene glycol), (Dermik), Penecort (with benzyl alcohol and propylene glycol), (Allergan), Preparation H Hydrocortisone (with parabens and propylene glycol), (Wyeth); 2.5% Anusol-HC (with benzyl alcohol and propylene glycol), (Pfizer), Hytone (with propylene glycol), (Dermik). Gel: 1% CortaGel Extra Strength, (Norstar).
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3533
Rectal: Cream: 1 Proctocort ( with benzyl alcohol and propylene glycol), (Monarch); Suspension: 100 mg/60 mL Cortenema ( with methylparaben), (Solvay), Hydrocortisone Enema, (Copley).
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3532
For more Formulations/Preparations (Complete) data for HYDROCORTISONE (14 total), please visit the HSDB record page.

9.4 General Manufacturing Information

EPA TSCA Commercial Activity Status
Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11.beta.)-: ACTIVE
RELATIVE ANTIINFLAMMATORY POTENCY= 1; RELATIVE SODIUM RETAINING POTENCY= 1. /FROM TABLE/
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1491

10 Identification

10.1 Analytic Laboratory Methods

REACTION RATE METHOD FOR DETERMINATION OF HYDROCORTISONE BASED UPON MODIFICATION OF WIDELY ACCEPTED BLUE TETRAZOLIUM REACTION. AN ANALYSIS TIME OF ONLY 30 SECONDS IS REQUIRED.
OTEIZA RM ET AL; ANAL CHEM 49: 1586 (1977)
Analyte: hydrocortisone; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 30/The National Formulary, NF 25; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p2291 (2007)
Analyte: hydrocortisone; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 30/The National Formulary, NF 25; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p2291 (2007)
Analyte: hydrocortisone; matrix: chemical purity; procedure: liquid chromatography with detection at 254 nm and comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 30/The National Formulary, NF 25; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p2291 (2007)
For more Analytic Laboratory Methods (Complete) data for HYDROCORTISONE (9 total), please visit the HSDB record page.

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

Note
Pictograms displayed are for 98.9% (270 of 273) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 1.1% (3 of 273) of reports.
Pictogram(s)
Health Hazard
Signal
Warning
GHS Hazard Statements

H361 (86.8%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H373 (31.5%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

Precautionary Statement Codes

P203, P260, P280, P318, P319, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 273 reports by companies from 33 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 3 of 273 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 32 notifications provided by 270 of 273 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Repr. 2 (86.8%)

STOT RE 2 (31.5%)

11.2 Handling and Storage

11.2.1 Storage Conditions

Commercially available preparations of hydrocortisone should be stored at a temperature less than 40 °C, preferably between 15-30 °C; freezing of the oral suspension and sterile suspensions should be avoided. Hydrocortisone tablets should be stored in well-closed containers. Reconstituted solutions of hydrocortisone sodium succinate should be stored at 25 °C or below.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3054

11.3 Exposure Control and Personal Protection

11.3.1 Allowable Tolerances

A tolerance is established for negligible residues of hydrocortisone (as hydrocortisone sodium succinate or hydrocortisone acetate) in milk at 10 parts per billion.
21 CFR 556.320; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 14, 2007: https://www.ecfr.gov

11.4 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11.beta.)-
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Hydrocortisone: Does not have an individual approval but may be used under an appropriate group standard

11.4.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl hydrocortisone valerate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Hydrocortisone Valerate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 15, 2007: https://www.fda.gov/cder/ob/
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl hydrocortisone butyrate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Hydrocortisone Butyrate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 15, 2007: https://www.fda.gov/cder/ob/
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl hydrocortisone acetate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Hydrocortisone Acetate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 15, 2007: https://www.fda.gov/cder/ob/
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl hydrocortisone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 15, 2007: https://www.fda.gov/cder/ob/
For more FDA Requirements (Complete) data for HYDROCORTISONE (9 total), please visit the HSDB record page.

11.5 Other Safety Information

Chemical Assessment

IMAP assessments - Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11.beta.)-: Human health tier I assessment

IMAP assessments - Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11.beta.)-: Environment tier I assessment

12 Toxicity

12.1 Toxicological Information

12.1.1 USGS Health-Based Screening Levels for Evaluating Water-Quality

Chemical
Hydrocortisone
Chemical Classes
Pharmaceutical
Reference
Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

12.1.2 Drug Induced Liver Injury

Compound
hydrocortisone
DILI Annotation
No-DILI-Concern
Label Section
No match
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

12.1.3 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Hydrocortisone (cortisol) is a normal component of breastmilk, but it has not been studied in milk after exogenous administration in pharmacologic amounts. Although it is unlikely that dangerous amounts of hydrocortisone would reach the infant, a better studied corticosteroid might be preferred. Maternal use of hydrocortisone as an enema would not be expected to cause any adverse effects in breastfed infants. Local maternal injections, such as for tendinitis, would not be expected to cause any adverse effects in breastfed infants. Medium to large doses of corticosteroids given systemically or injected into joints or the breast have been reported to cause temporary reduction of lactation. See also Hydrocortisone, Topical.

Cortisol in breastmilk might have a role in intestinal maturation, the intestinal microbiome, growth, body composition or neurodevelopment, but adequate studies are lacking. Concentrations follow a diurnal rhythm, with the highest concentrations in the morning at about 7:00 am and the lowest concentrations in the late afternoon and evening. Cortisol concentration in milk also increase with infant age and decrease with complementary feeding and infant illness. Cortisol in milk may protect against later infant obesity, especially in girls; however, in another study, milk glucocorticoid levels were positively associated with percent fat mass, adiposity and head circumference at 1 year of age. Maternal stress can increase breastmilk cortisol levels, especially with preterm births. Some information indicates that maternal adverse childhood experiences may decrease cortisol concentration in their breastmilk.

◉ Effects in Breastfed Infants

None reported with any systemic corticosteroid.

◉ Effects on Lactation and Breastmilk

Published information on the effects of hydrocortisone on serum prolactin or on lactation in nursing mothers was not found as of the revision date. Medium to large doses of corticosteroids given systemically or injected into joints or the breast have been reported to cause temporary reduction of lactation.

A study of 46 women who delivered an infant before 34 weeks of gestation found that a course of another corticosteroid (betamethasone, 2 intramuscular injections of 11.4 mg of betamethasone 24 hours apart) given between 3 and 9 days before delivery resulted in delayed lactogenesis II and lower average milk volumes during the 10 days after delivery. Milk volume was not affected if the infant was delivered less than 3 days or more than 10 days after the mother received the corticosteroid. An equivalent dosage regimen of hydrocortisone might have the same effect.

A study of 87 pregnant women found that betamethasone given as above during pregnancy caused a premature stimulation of lactose secretion during pregnancy. Although the increase was statistically significant, the clinical importance appears to be minimal. An equivalent dosage regimen of hydrocortisone might have the same effect.

◉ Summary of Use during Lactation

Topical hydrocortisone has not been studied during breastfeeding. Since only extensive application of the most potent corticosteroids may cause systemic effects in the mother, it is unlikely that short-term application of topical hydrocortisone would pose a risk to the breastfed infant by passage into breastmilk. However, it would be prudent to use the least potent drug on the smallest area of skin possible. It is important to ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Current guidelines allow topical corticosteroids to be applied to the nipples just after nursing for eczema, with the nipples cleaned gently before nursing. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking. Maternal use rectally with a cream or by suppository poses little to no risk to the breastfed infant.

◉ Effects in Breastfed Infants

Topical application of a corticosteroid with relatively high mineralocorticoid activity (isofluprednone acetate) to the mother's nipples resulted in prolonged QT interval, cushingoid appearance, severe hypertension, decreased growth and electrolyte abnormalities in her 2-month-old breastfed infant. The mother had used the cream since birth for painful nipples.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

12.1.4 Acute Effects

12.1.5 Interactions

Hydrocortisone (80 mg/kg body weight, intraperitoneally for 4 days), both alone and in combination with acetylsalicylic acid (160 mg/kg body weight, orally, for 4 days), decreased acetylsalicylic acid general and specific toxicity via metabolic modulation of drug-metabolizing enzyme systems (intestinal acetylsalicylic acid-esterase and hepatic UDP-glucuronyltransferase) and did not change the acetylsalicylic acid analgesic effect.
Tantcheva L et al; Gen Pharmacol 28 (1): 123-8 (1997)
The effect of glucocorticoids on oral anticoagulant therapy is variable, and the efficacy of oral anticoagulants has been reported to be enhanced or diminished with concomitant glucocorticoid administration. Patients receiving glucocorticoids and oral anticoagulants concomitantly should be monitored (e.g., using coagulation indices) in order to maintain desired anticoagulant effect. /Corticosteroids/
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3036
Estrogens may potentiate effects of hydrocortisone, possibly by increasing the concentration of transcortin and thus decreasing the amount of hydrocortisone available to be metabolized.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3036
Potassium-depleting diuretics (e.g., thiazides, furosemide, ethacrynic acid) and other drugs that deplete potassium, such as amphotericin B, may enhance the potassium-wasting effect of glucocorticoids. Serum potassium should be closely monitored in patients receiving glucocorticoids and potassium-depleting drugs. /Corticosteroids/
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3036
For more Interactions (Complete) data for HYDROCORTISONE (7 total), please visit the HSDB record page.

12.1.6 Antidote and Emergency Treatment

The items in this list /including hydrocortisone cream/ usually have little or no effect in small ingestions. In moderate to large ingestions, gastrointestinal effects such as diarrhea, constipation, stomach cramps, and vomiting may occur. The effects are usually mild and rarely require medical intervention. /From table; nontoxic or minimally toxic household products/
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 5th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2007., p. 288
For chronic topical overdose: Since there is no specific antidote available, treatment is symptomatic, supportive, and consists of discontinuance of topical corticosteroid therapy. Gradual withdrawal of the preparation may be necessary. For acute oral overdose: Since there is no specific antidote available and serious adverse effects are unlikely, treatment consists of dilution with fluids. /Corticosteroids (topical)/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 921

12.1.7 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ Glucocorticoids should be used with caution in patients with seizure disorders, renal insufficiency, osteoporosis, or herpes simplex infections of the eye; some manufacturers state that glucocorticoids should not be used in patients with active ocular herpes simplex infections /SRP: due to the risk of corneal ulceration/. /Corticosteroids/
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3035
/CASE REPORTS/ A 66-year-old man who complained of generalized muscle weakness, shallow respiration, and palpitations after receiving high-dose intravenous hydrocortisone (total dose, 2400 mg over 4 days) to treat a severe asthma attack /is described/. During this therapy, there was a weight gain of 1.0 kg. An electrocardiogram revealed ventricular arrhythmia with frequent premature ventricular contractions. Hypokalemia was profound, with plasma potassium (K+) concentration of 1.7 mEq/L, and associated with renal potassium wasting, as evidenced by a transtubular potassium concentration gradient of 12; metabolic alkalosis (plasma hydrocortisone O3-, 37 mEq/L) was also present. When treated with spironolactone, KCl supplementation, and substitution of hydrocortisone with prednisolone, his plasma K+ concentration rapidly normalized, metabolic alkalosis was corrected, and arrhythmia disappeared within 3 days. Because of unwanted mineralocorticoid side-effects, high-dose hydrocortisone may cause life-threatening hypokalemia in asthmatic patients. Because of these potential risks, plasma acid-base and electrolyte concentrations should be monitored frequently in any patient treated with high-dose hydrocortisone.
Tsai WS et al; Am J Med Sci 327 (3): 152-5 (2004)
/CASE REPORTS/ A 62-year-old asthmatic patient with evidence of aspirin sensitivity ... /was/ administered 100 mg of hydrocortisone-21-hemisuccinate dissolved in 100 mL 0.9% sodium chloride solution for perioperative corticoid substitution. The patient immediately developed severe bronchospasm and anaphylactic shock requiring intubation and mechanical ventilation. He received adrenaline, isoflurane, ketamine and inhalational fenoterol. He then developed atrioventricular block type III for which he was transcutaneously paced. Subsequently he was tested via skin prick tests, intracutaneous tests and IV-challenges resulting in the patient having positive reactions to hydrocortisone-21-hemisuccinate. /Hydrocortisone-21-hemisuccinate/
Holz W et al; Anaesthesist 51 (3): 187-90 (2002)
/CASE REPORTS/ Glucocorticoids may indirectly cause convulsions by the induction of electrolytes abnormalities, severe hypertension, or severe hyperglycemia. These agents may rarely cause convulsions by a direct toxicity to the central nervous system (CNS). We describe a 23-yr-old patient with Crohn's disease in whom generalized convulsions developed on two occasions while receiving intravenous hydrocortisone.
Odeh M et al; J Toxicol Clin Toxicol 41 (7): 995-7 (2003)
For more Human Toxicity Excerpts (Complete) data for HYDROCORTISONE (8 total), please visit the HSDB record page.

12.1.8 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The effects of hydrocortisone during the prenatal period and its later repercussion on reproductive aspects of female rats /were investigated/. Pregnant rats were treated (s.c.) with hydrocortisone acetate, at 1.5 mg/day on the 17th, 18th, and 19th days of pregnancy. Although the present study was not intended to identify mechanisms of toxicity, the treatment with hydrocortisone in the last period of pregnancy presented no signs of toxicity. The efficacy of the hydrocortisone in reducing the adrenal wet mass and plasma corticosterone levels immediately after delivery in both the treated mothers and in respective pups at birth may indicate impairment of the hypothalamus-pituitary-adrenal axis. In addition, the treatment with hydrocortisone did not interfere in the development of the female descendants until puberty. However, it affected the estrous cycle and fertility. Probably, the prenatal exposure to corticosteroids had altered at least partially the hypothalamus-pituitary-gonadal axis, resulting in the damages observed in adult life. These results indicate that the use of the hydrocortisone at a dose that apparently does not endanger the neonate led to undesirable effects in the adult reproductive phase, resulting in later deleterious alteration of the reproductive physiology in female rats. /Hydrocortisone acetate/
Piffer RC, Pereira OC; Comp Biochem Physiol C Toxicol Pharmacol 139 (1-3): 11-6 (2004)
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The aim of the present study was to investigate the effects of hydrocortisone during the prenatal period and its later repercussions on the fertility and sexual behavior of male rats. Pregnant rats were treated (sc) with hydrocortisone acetate, at 1.5 mg/day on the 17th, 18th, and 19th days of gestation. Decreased body weight and no alteration in anogenital distance were observed in male offspring. Adulthood, presented reductions of body weight, plasma testosterone levels, and seminal-vesicle wet weight without secretion as well as no alteration in the wet weights of the testes, epididymis, and seminal vesicle with secretion in the treated group. Males exposed to hydrocortisone during the prenatal period were able to mate with normal females, which became pregnant but exhibited an increased number of post-implantation losses. In spite of this, these treated males exhibited decreased male sexual behavior and the appearance of female sexual behavior after these male rats were castrated and pretreated with exogenous estrogen. These results indicate that exposure to hydrocortisone in the later stages of pregnancy may have a long-term effect on the fertility and sexual behavior of male rats, suggesting an incomplete masculinization and defeminization of the central nervous system.
Pereira OC et al; Regul Toxicol Pharmacol 38 (1): 36-42 (2003)

12.1.9 Populations at Special Risk

Because cortisone has been reported rarely to increase blood coagulability and to precipitate intravascular thrombosis, thromboembolism, and thrombophlebitis, corticosteroids should be used with caution in patients with thromboembolic disorders. Glucocorticoids should be used with caution in patients with seizure disorders, renal insufficiency, osteoporosis, or herpes simplex infections of the eye; some manufacturers state that glucocorticoids should not be used in patients with active ocular herpes simplex infections. /Corticosteroids/
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3035
Because an apparent association has been suggested between use of corticosteroids and left ventricular free-wall rupture after a recent myocardial infarction, corticosteroids should be used with extreme caution in these patients. /Corticosteroids/
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3034
This study examined the hypothesis/ that subjects with posttraumatic stress disorder, as compared to nonpsychiatric controls, would show greater impairments in verbal declarative memory and working memory, but not attention, following exogenous glucocorticoid administration. ... The hydrocortisone administration led to impairment in working memory in the group of subjects with posttraumatic stress disorder, but not in the control subject group.
Grossman R et al; Ann N Y Acad Sci 1071: 410-21(2006)

12.1.10 Protein Binding

Corticosteroids are generally bound to corticosteroid binding globulin and serum albumin in plasma. Hydrocortisone is 90.1% bound to proteins in plasma, with 56.2% bound to albumin.

12.2 Ecological Information

12.2.1 Environmental Fate / Exposure Summary

Hydrocortisone's production and use as an antiinflammatory may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.3X10-13 mm Hg at 25 °C indicates hydrocortisone will exist solely in the particulate phase in the atmosphere. Particulate-phase hydrocortisone will be removed from the atmosphere by wet or dry deposition. Hydrocortisone does not absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, hydrocortisone is expected to have moderate mobility based upon an estimated Koc of 180. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 5.8X10-8 atm-cu m/mole. Biodegradation data were not available. If released into water, hydrocortisone is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to hydrocortisone may occur through inhalation and dermal contact with this compound at workplaces where hydrocortisone is produced or used. Use data indicate that the general population may be exposed to hydrocortisone via dermal contact with this compound and other consumer products containing hydrocortisone. (SRC)

12.2.2 Artificial Pollution Sources

Hydrocortisone's production and use as an antiinflamatory(1) may result in its release to the environment through various waste streams(SRC).
(1) Lewis RJ, Sr; Hawley's Condensed Chemical Dictionary 14th Ed. John Wiley & Sons, Inc. New York, NY p. 585 (2001)

12.2.3 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 180(SRC), determined from a log Kow of 1.61(2) and a regression-derived equation(3), indicates that hydrocortisone is expected to have moderate mobility in soil(SRC). Volatilization of hydrocortisone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.8X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Hydrocortisone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.3X10-13 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2007).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 174 (1995)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(4) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(5) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 180(SRC), determined from a log Kow of 1.61(2) and a regression-derived equation(3), indicates that hydrocortisone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.8X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2007).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 174 (1995)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990)
(4) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(5) Franke C et al; Chemosphere 29: 1501-14 (1994)
(6) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), hydrocortisone, which has an estimated vapor pressure of 1.3X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase hydrocortisone may be removed from the air by wet or dry deposition(SRC). Hydrocortisone does not absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(5).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) O'Neil MJ, ed: The Merck Index. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., p. 855 (2001)
(5) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)

12.2.4 Environmental Abiotic Degradation

Hydrocortisone is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze readily under environmental conditions(1). Hydrocortisone does not absorb at wavelengths >290 nm(2) and therefore is not expected to be susceptible to direct photolysis by sunlight(1).
(1) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)
(2) O'Neil MJ, ed: The Merck Index. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., p. 855 (2001)

12.2.5 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for hydrocortisone(SRC), using a log Kow of 1.61(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 174 (1995)
(2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

12.2.6 Soil Adsorption / Mobility

The Koc of hydrocortisone is estimated as 180(SRC), using a log Kow of 1.61(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that hydrocortisone is expected to have moderate mobility in soil.
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 174 (1995)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(3) Swann RL et al; Res Rev 85: 17-28 (1983)

12.2.7 Volatilization from Water / Soil

The Henry's Law constant for hydrocortisone is estimated as 5.8X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that hydrocortisone is expected to be essentially nonvolatile from water surfaces(2). Hydrocortisone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.3X10-13 mm Hg(SRC), determined from a fragment constant method(3).
(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)
(3) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

12.2.8 Environmental Water Concentrations

While data specific to hydrocortisone were not located(SRC, 2007), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).
(1) Heberer T; Tox Lett 131: 5-17 (2002)
(2) Koplin DW et al; Environ Sci Toxicol 36: 1202-211 (2002)

12.2.9 Probable Routes of Human Exposure

NIOSH (NOES Survey 1981-1983) has statistically estimated that 36,900 workers (21,576 of these are female) are potentially exposed to hydrocortisone in the US(1). Occupational exposure to hydrocortisone may occur through inhalation and dermal contact with this compound at workplaces where hydrocortisone is produced or used(SRC). Use data indicate that the general population may be exposed to hydrocortisone via dermal contact with this compound and other consumer products containing hydrocortisone(SRC).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available at https://www.cdc.gov/noes/ as of Jan 19, 2007.

13 Associated Disorders and Diseases

Disease
Bipolar disorder
References
Disease
Tic disorder
References
PubMed: 17665285
Disease
ACTH deficiency, isolated
References

PubMed: 25870516, 210721

MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)

Disease
Adrenal hypoplasia
References
MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)
Disease
Apparent mineralocorticoid excess
References
PubMed: 870517
Disease
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
References
Disease
Aromatase deficiency
References
PubMed: 9177373
Disease
3-Hydroxy-3-Methylglutaryl-CoA Synthase Deficiency
References
Disease
3-Hydroxyacyl-CoA dehydrogenase deficiency
References
Disease
Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis
References
Disease
Congenital Adrenal Hyperplasia, due to 17-Hydroxylase-Deficiency
References
Disease
Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete
References
PubMed: 18182448
Disease
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
References

PubMed: 6157502, 11129331, 28583327, 15505778, 25557019, 23705938, 1886403, 12072887, 19893767

MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)

Disease
Bartter Syndrome, Type 2, Antenatal
References
PubMed: 26069767
Disease
Glucocorticoid resistance
References
PubMed: 23076843
Disease
Proprotein Convertase 1/3 Deficiency
References
PubMed: 7477119
Disease
Lipoid Congenital Adrenal Hyperplasia
References
Disease
Corticosterone methyl oxidase I deficiency
References
PubMed: 27125267
Disease
Benign gynecological diseases
References
PubMed: 10585175
Disease
Functional hypothalamic amenorrhea
References
PubMed: 16464944
Disease
Stress
References
PubMed: 15257879
Disease
Anorexia nervosa
References
Disease
Rheumatoid arthritis
References

PubMed: 6589104, 16277678, 15338487, 10361015, 15249323

Tie-juan ShaoZhi-xing HeZhi-jun XieHai-chang LiMei-jiao WangCheng-ping Wen. Characterization of ankylosing spondylitis and rheumatoid arthritis using 1H NMR-based metabolomics of human fecal extracts. Metabolomics. April 2016, 12:70: https://link.springer.com/article/10.1007/s11306-016-1000-2

Disease
Leptin Deficiency or Dysfunction
References
PubMed: 10486419

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Wiley References

14.6 Chemical Co-Occurrences in Literature

14.7 Chemical-Gene Co-Occurrences in Literature

14.8 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 FDA Orange Book Patents

15.4 Chemical Co-Occurrences in Patents

15.5 Chemical-Disease Co-Occurrences in Patents

15.6 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Protein Bound 3D Structures

16.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

16.2 Chemical-Target Interactions

16.3 Drug-Drug Interactions

16.4 Drug-Food Interactions

Avoid alcohol.

16.5 Pathways

17 Biological Test Results

17.1 BioAssay Results

18 Taxonomy

Zebrafish Pathway Metabolite MetFrag Local CSV (Beta) | DOI:10.5281/zenodo.3457553
The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 LIPID MAPS Classification

19.5 KEGG: Metabolite

19.6 KEGG: Lipid

19.7 KEGG: Drug

19.8 KEGG: USP

19.9 KEGG: ATC

19.10 KEGG: Target-based Classification of Drugs

19.11 KEGG: JP15

19.12 KEGG: Risk Category of Japanese OTC Drugs

19.13 KEGG: OTC drugs

19.14 KEGG: Drug Groups

19.15 KEGG: Drug Classes

19.16 WHO ATC Classification System

19.17 FDA Pharm Classes

19.18 ChemIDplus

19.19 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

19.20 ChEMBL Target Tree

19.21 UN GHS Classification

19.22 EPA CPDat Classification

19.23 NORMAN Suspect List Exchange Classification

19.24 CCSBase Classification

19.25 EPA DSSTox Classification

19.26 Consumer Product Information Database Classification

19.27 EPA TSCA and CDR Classification

19.28 LOTUS Tree

19.29 EPA Substance Registry Services Tree

19.30 MolGenie Organic Chemistry Ontology

20 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11.beta.)-
    https://services.industrialchemicals.gov.au/search-assessments/
    Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11.beta.)-
    https://services.industrialchemicals.gov.au/search-inventory/
  2. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  3. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  5. DTP/NCI
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  6. EPA Chemicals under the TSCA
    Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11.beta.)-
    https://www.epa.gov/chemicals-under-tsca
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  7. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  8. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
  9. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  10. Hazardous Substances Data Bank (HSDB)
  11. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  12. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  13. BindingDB
    LICENSE
    All data curated by BindingDB staff are provided under the Creative Commons Attribution 3.0 License (https://creativecommons.org/licenses/by/3.0/us/).
    https://www.bindingdb.org/rwd/bind/info.jsp
    (1S,2R,10S,11S,14R,15S,17S)-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
    https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=13775
  14. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  15. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  16. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
    The Guide to PHARMACOLOGY database is licensed under the Open Data Commons Open Database License (ODbL) https://opendatacommons.org/licenses/odbl/. Its contents are licensed under a Creative Commons Attribution-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-sa/4.0/)
    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  17. Therapeutic Target Database (TTD)
  18. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  19. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Hydrocortisone
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  20. ChEBI
  21. FDA Pharm Classes
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  22. LOTUS - the natural products occurrence database
    LICENSE
    The code for LOTUS is released under the GNU General Public License v3.0.
    https://lotus.nprod.net/
  23. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  24. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  25. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  26. Consumer Product Information Database (CPID)
    LICENSE
    Copyright (c) 2024 DeLima Associates. All rights reserved. Unless otherwise indicated, all materials from CPID are copyrighted by DeLima Associates. No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://www.whatsinproducts.com/contents/view/1/6
    Consumer Products Category Classification
    https://www.whatsinproducts.com/
  27. Crystallography Open Database (COD)
    LICENSE
    All data in the COD and the database itself are dedicated to the public domain and licensed under the CC0 License. Users of the data should acknowledge the original authors of the structural data.
    https://creativecommons.org/publicdomain/zero/1.0/
  28. DailyMed
  29. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  30. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency's (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
  31. Drugs and Lactation Database (LactMed)
  32. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  33. WHO Model Lists of Essential Medicines
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) license.
    https://www.who.int/about/policies/publishing/copyright
  34. ECI Group, LCSB, University of Luxembourg
    LICENSE
    Data: CC-BY 4.0; Code: Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Cortisol
  35. Natural Product Activity and Species Source (NPASS)
  36. EPA Chemical and Products Database (CPDat)
  37. EU Clinical Trials Register
  38. FDA Approved Animal Drug Products (Green Book)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  39. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  40. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  41. FDA Medication Guides
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  42. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  43. MassBank Europe
    (8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
    https://massbank.eu/MassBank/Result.jsp?inchikey=JYGXADMDTFJGBT-VWUMJDOOSA-N
  44. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  45. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  46. SpectraBase
    4-Pregnen-11β,17,21-triol-3, 20-dione
    https://spectrabase.com/spectrum/4R0FNbbkQuI
    11-BETA-17,21-TRIHYDROXYPREGN-4-EN-3,20-DION,(CORTISOL)
    https://spectrabase.com/spectrum/IQaopr5BkXP
    4-Pregnen-11β,17,21-triol-3,20-dione
    https://spectrabase.com/spectrum/FhOIEJ8nutu
  47. Japan Chemical Substance Dictionary (Nikkaji)
  48. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
    Drugs listed in the Japanese Pharmacopoeia
    http://www.genome.jp/kegg-bin/get_htext?br08311.keg
    Risk category of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08312.keg
    Classification of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08313.keg
  49. LIPID MAPS
    Lipid Classification
    https://www.lipidmaps.org/
  50. MarkerDB
    LICENSE
    This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
    https://markerdb.ca/
  51. Metabolomics Workbench
  52. NIPH Clinical Trials Search of Japan
  53. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  54. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  55. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  56. Protein Data Bank in Europe (PDBe)
  57. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  58. Rhea - Annotated Reactions Database
    LICENSE
    Rhea has chosen to apply the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). This means that you are free to copy, distribute, display and make commercial use of the database in all legislations, provided you credit (cite) Rhea.
    https://www.rhea-db.org/help/license-disclaimer
  59. Springer Nature
  60. SpringerMaterials
  61. The Cambridge Structural Database
  62. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  63. USGS Health-Based Screening Levels for Evaluating Water-Quality Data
  64. Wikidata
  65. Wikipedia
  66. Wiley
  67. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  68. PubChem
  69. GHS Classification (UNECE)
  70. EPA Substance Registry Services
  71. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  72. PATENTSCOPE (WIPO)
  73. NCBI
CONTENTS