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Identification
Name Fludrocortisone
Accession Number DB00687 (APRD00756, DB02478)
Type small molecule
Groups approved
Description

A synthetic mineralocorticoid with anti-inflammatory activity. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • 9 .Alpha. Ff
  • 9 Alpha Ff
  • 9 alpha-Fludrocortisone
  • 9 alpha-Fluorocortisol
  • 9.Alpha.-Fluorocortisol
  • 9.Alpha.-Fluorohydrocortisone
  • Alflorone
  • Astonin-H
  • F-COL
  • F-Cortef
  • Florinef
  • Fludrocortisona [INN-Spanish]
  • Fludrocortisone Acetate
  • Fludrocortisonum [INN-Latin]
  • Fludrocortone
  • Fludrone
  • Fludronef
  • Fluodrocortisone
  • Fluohydrisone
  • Fluohydrocortisone
  • Fluorocortisol
  • Fluorocortisone
  • ZK5
Brand name mixtures Not Available
Categories
  • Anti-inflammatory Agents
  • Adrenergic Agents
CAS number 127-31-1
Weight Average: 380.4504
Monoisotopic: 380.199902243
Chemical Formula C21H29FO5
InChI Key InChIKey=AAXVEMMRQDVLJB-BULBTXNYSA-N
InChI
InChI=1S/C21H29FO5/c1-18-7-5-13(24)9-12(18)3-4-15-14-6-8-20(27,17(26)11-23)19(14,2)10-16(25)21(15,18)22/h9,14-16,23,25,27H,3-8,10-11H2,1-2H3/t14-,15-,16-,18-,19-,20-,21-/m0/s1
Plain Text
IUPAC Name
(1R,2S,10S,11S,14R,15S,17S)-1-fluoro-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
SMILES
[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)CC[C@]12C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Alkyl Halides
  • Alcohols and Polyols
  • Cyclohexenes and Derivatives
  • Ketones
Pharmacology
Indication For partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison's disease and for the treatment of salt-losing adrenogenital syndrome.
Pharmacodynamics Fludrocortisone is a synthetic adrenocortical steroid possessing very potent mineralocorticoid properties and high glucocorticoid activity. It is indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome. The physiologic action of fludrocortisone acetate is similar to that of hydrocortisone. However, the effects of fludrocortisone acetate, particularly on electrolyte balance, but also on carbohydrate metabolism, are considerably heightened and prolonged. Mineralocorticoids act on the distal tubules of the kidney to enhance the reabsorption of sodium ions from the tubular fluid into the plasma; they increase the urinary excretion of both potassium and hydrogen ions.
Mechanism of action Fludrocortisone binds the mineralocorticoid receptor (aldosterone receptor). This binding (or activation of the mineralocorticoid receptor by fludrocortisone) in turn causes an increase in ion and water transport and thus raises extracellular fluid volume and blood pressure and lowers potassium levels.
Absorption Not Available
Volume of distribution Not Available
Protein binding High
Metabolism

Hepatic, some renal.
Route of elimination Not Available
Half life 3.5 hours
Clearance Not Available
Toxicity Effects of overexposure include irritation, cardiac edema, increased blood volume, hypertension, cardiac arrhythmias, enlargement of the heart, headaches, and weakness of the extremities.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • King pharmaceuticals inc
  • Barr laboratories inc
  • Impax laboratories inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Fludrocortisone acetate powder 73.14 USD g
Florinef acetate 0.1 mg tablet 1.49 USD tablet
Fludrocortisone Acetate 0.1 mg tablet 0.81 USD tablet
Fludrocortisone 0.1 mg tablet 0.75 USD tablet
Florinef 0.1 mg Tablet 0.25 USD tablet
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility 140 mg/L PhysProp
logP 0.3 PhysProp
logS -3.43 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 2.24e-01 g/l ALOGPS
logP 1.35 ALOGPS
logP 1.32 ChemAxon Molconvert
logS -3.23 ALOGPS
pKa 13.50 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 94.83 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 96.93 ChemAxon Molconvert
polarizability 39.60 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07004 Link_out
PubChem Compound 31378 Link_out
PubChem Substance 46508616 Link_out
ChemSpider 29111 Link_out
ChEBI 50885 Link_out
ChEMBL 50885 Link_out
Therapeutic Targets Database DAP001105 Link_out
PharmGKB PA449657 Link_out
Drug Product Database 2086026 Link_out
RxList http://www.rxlist.com/cgi/generic/fludro.htm Link_out
Drugs.com http://www.drugs.com/cdi/fludrocortisone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Fludrocortisone Link_out
ATC Codes
  • H02AA02
AHFS Codes
  • 68:04.00
PDB Entries
FDA label Not Available
MSDS show (73 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid excess salt/sodium unless otherwise instructed by your physician.
  • Take with food to reduce irritation.
Targets

1. Mineralocorticoid receptor

Pharmacological action: yes
Actions: agonist

Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels

Organism class: human
UniProt ID: P08235 Link_out
Gene: NR3C2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Otte C, Jahn H, Yassouridis A, Arlt J, Stober N, Maass P, Wiedemann K, Kellner M: The mineralocorticoid receptor agonist, fludrocortisone, inhibits pituitary-adrenal activity in humans after pre-treatment with metyrapone. Life Sci. 2003 Aug 22;73(14):1835-45. Pubmed
  2. Oelkers W, Buchen S, Diederich S, Krain J, Muhme S, Schoneshofer M: Impaired renal 11 beta-oxidation of 9 alpha-fluorocortisol: an explanation for its mineralocorticoid potency. J Clin Endocrinol Metab. 1994 Apr;78(4):928-32. Pubmed
  3. Young MJ, Funder JW: Mineralocorticoids, salt, hypertension: effects on the heart. Steroids. 1996 Apr;61(4):233-5. Pubmed
  4. Kingsley-Kallesen M, Mukhopadhyay SS, Wyszomierski SL, Schanler S, Schutz G, Rosen JM: The mineralocorticoid receptor may compensate for the loss of the glucocorticoid receptor at specific stages of mammary gland development. Mol Endocrinol. 2002 Sep;16(9):2008-18. Pubmed
  5. Buckley TM, Mullen BC, Schatzberg AF: The acute effects of a mineralocorticoid receptor (MR) agonist on nocturnal hypothalamic-adrenal-pituitary (HPA) axis activity in healthy controls. Psychoneuroendocrinology. 2007 Jul 29;. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Glucocorticoid receptor

Pharmacological action: unknown
Actions: agonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth

Organism class: human
UniProt ID: P04150 Link_out
Gene: NR3C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Trune DR, Kempton JB: Low dose combination steroids control autoimmune mouse hearing loss. J Neuroimmunol. 2010 Aug 26. Pubmed

3. Androgen receptor

Pharmacological action: unknown
Actions: agonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Activated, but not phosphorylated, by HIPK3

Organism class: human
UniProt ID: P10275 Link_out
Gene: AR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Krishnan AV, Zhao XY, Swami S, Brive L, Peehl DM, Ely KR, Feldman D: A glucocorticoid-responsive mutant androgen receptor exhibits unique ligand specificity: therapeutic implications for androgen-independent prostate cancer. Endocrinology. 2002 May;143(5):1889-900. Pubmed
  2. Matias PM, Carrondo MA, Coelho R, Thomaz M, Zhao XY, Wegg A, Crusius K, Egner U, Donner P: Structural basis for the glucocorticoid response in a mutant human androgen receptor (AR) derived from an androgen-independent prostate cancer. J Med Chem. 2002 Mar 28;45(7):1439-46. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on July 13, 2011 10:11

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.