Identification

Name
Fludrocortisone
Accession Number
DB00687  (APRD00756, DB02478)
Type
Small Molecule
Groups
Approved, Investigational
Description

A synthetic mineralocorticoid with anti-inflammatory activity. [PubChem]

Structure
Thumb
Synonyms
  • 9alpha-FLUOROCORTISOL
  • Fludrocortison
  • Fludrocortisona
  • Fludrocortisone
  • Fludrocortisonum
  • Fluohydrocortisone
External IDs
StC 1400
Product Ingredients
IngredientUNIICASInChI Key
Fludrocortisone AcetateV47IF0PVH4514-36-3SYWHXTATXSMDSB-GSLJADNHSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FlorinefTablet0.1 mgOralPaladin Labs Inc1995-12-31Not applicableCanada
Florinef AcetateTablet.1 mg/1OralMonarch Pharmaceuticals, Inc.1955-08-182007-09-20Us
Florinef Acetate 0.1mgTablet.1 mgOralSquibb Canada Inc., Division Of Bristol Myers Squibb Canada Inc.1958-12-311997-08-14Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Fludrocortisone AcetateTablet0.1 mg/1OralRemedy Repack2011-10-032012-10-03Us
Fludrocortisone AcetateTablet0.1 mg/1OralPhysicians Total Care, Inc.2005-10-06Not applicableUs54868 544620180906 25352 v6ed2v
Fludrocortisone AcetateTablet0.1 mg/1OralTeva Pharmaceuticals USA, Inc.2003-02-14Not applicableUs00555 0997 02 nlmimage10 b107d88e
Fludrocortisone AcetateTablet0.1 mg/1OralPd Rx Pharmaceuticals, Inc.2003-02-14Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralImpax Generics2002-03-18Not applicableUs00115 7033 01 nlmimage10 0f4a07f0
Fludrocortisone AcetateTablet0.1 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs2002-03-30Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralCardinal Health2008-05-09Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralAv Kare, Inc.2009-10-20Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralAmerincan Health Packaging2008-09-09Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralWest Ward Pharmaceutical2011-07-22Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Florinef AcetateFludrocortisone Acetate (0.1 mg/1)TabletOralPhysicians Total Care, Inc.1993-11-022011-05-31Us
International/Other Brands
Adixone (Genopharm) / Astonin (Merck) / Cortineff (Polfa Pabianice) / Florinef Acetaat (Bristol-Myers Squibb) / Florinefe (Bristol-Myers Squibb) / Fludrocortison (Bristol-Myers Squibb) / Lonikan (Merck)
Categories
UNII
U0476M545B
CAS number
127-31-1
Weight
Average: 380.4504
Monoisotopic: 380.199902243
Chemical Formula
C21H29FO5
InChI Key
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
IUPAC Name
(1R,2S,10S,11S,14R,15S,17S)-1-fluoro-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]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

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.

Associated Conditions
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.

TargetActionsOrganism
AMineralocorticoid receptor
agonist
Human
UGlucocorticoid receptor
agonist
Human
UAndrogen receptor
agonist
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Fludrocortisone.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Fludrocortisone.
1-TestosteroneThe risk or severity of edema formation can be increased when 1-Testosterone is combined with Fludrocortisone.
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Fludrocortisone.
16-BromoepiandrosteroneThe risk or severity of edema formation can be increased when 16-Bromoepiandrosterone is combined with Fludrocortisone.
19-norandrostenedioneThe risk or severity of edema formation can be increased when 19-norandrostenedione is combined with Fludrocortisone.
1alpha-Hydroxyvitamin D5The therapeutic efficacy of 1alpha-Hydroxyvitamin D5 can be decreased when used in combination with Fludrocortisone.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with 2-Methoxyethanol.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Fludrocortisone.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Fludrocortisone.
Food Interactions
  • Avoid excess salt/sodium unless otherwise instructed by your physician.
  • Take with food to reduce irritation.

References

Synthesis Reference

U.S. Patent 2,957,013

General References
Not Available
External Links
Human Metabolome Database
HMDB0014825
KEGG Compound
C07004
PubChem Compound
31378
PubChem Substance
46508616
ChemSpider
29111
ChEBI
50885
ChEMBL
CHEMBL1201388
Therapeutic Targets Database
DAP001105
PharmGKB
PA164743961
IUPHAR
2873
Guide to Pharmacology
GtP Drug Page
HET
ZK5
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Fludrocortisone
ATC Codes
S01CA06 — Fludrocortisone and antiinfectivesS02CA07 — Fludrocortisone and antiinfectivesS03CA05 — Fludrocortisone and antiinfectivesH02AA02 — Fludrocortisone
AHFS Codes
  • 68:04.00 — Adrenals
PDB Entries
1gs4
MSDS
Download (73 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers / Pharmacodynamics1
1CompletedTreatmentDepression1
1CompletedTreatmentIdiopathic orthostatic hypotension / Multiple System Atrophy (MSA) / Parkinson's Disease (PD)1
1RecruitingNot AvailableHealthy Volunteers1
1, 2TerminatedBasic ScienceRenin Angiotensin1
2Active Not RecruitingTreatmentAutonomic Disturbances in Parkinson's Disease1
2CompletedBasic ScienceHealthy Volunteers1
2Not Yet RecruitingTreatmentCongenital Adrenal Hyperplasia (CAH)1
2Not Yet RecruitingTreatmentShock, Septic1
2RecruitingTreatmentPartial Mineralocorticoid Deficiency1
3CompletedTreatmentShock, Septic2
3WithdrawnTreatmentShock, Septic1
4CompletedTreatmentSyncope, Vasovagal, Neurally-Mediated1
4Unknown StatusDiagnosticHigh Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableAcidosis, Renal Tubular / Calcium Nephrolithiasis / Vacuolar Proton-Translocating ATPases1
Not AvailableCompletedTreatmentMajor Depressive Disorder (MDD)1
Not AvailableCompletedTreatmentIdiopathic orthostatic hypotension1
Not AvailableRecruitingBasic ScienceMajor Depressive Disorder (MDD)1
Not AvailableRecruitingTreatmentHearing Loss, Sensorineural1
Not AvailableWithdrawnNot AvailableDiabetes, Diabetes Mellitus Type 11

Pharmacoeconomics

Manufacturers
  • King pharmaceuticals inc
  • Barr laboratories inc
  • Impax laboratories inc
Packagers
  • Amerisource Health Services Corp.
  • Avkare Incorporated
  • Barr Pharmaceuticals
  • Bristol-Myers Squibb Co.
  • Cardinal Health
  • E.R. Squibb and Sons LLC
  • Global Pharmaceuticals
  • Heartland Repack Services LLC
  • Impax Laboratories Inc.
  • Kaiser Foundation Hospital
  • Medisca Inc.
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
TabletOral0.1 mg
TabletOral.1 mg/1
TabletOral.1 mg
TabletOral0.1 mg/1
Prices
Unit descriptionCostUnit
Fludrocortisone acetate powder73.14USD g
Florinef acetate 0.1 mg tablet1.49USD tablet
Fludrocortisone Acetate 0.1 mg tablet0.81USD tablet
Fludrocortisone 0.1 mg tablet0.75USD tablet
Florinef 0.1 mg Tablet0.25USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility140 mg/L (at 25 °C)MERCK INDEX (1996)
logP1.67HANSCH,C ET AL. (1995)
logS-3.43ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.224 mg/mLALOGPS
logP1.35ALOGPS
logP1.32ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)12.55ChemAxon
pKa (Strongest Basic)-3.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity96.93 m3·mol-1ChemAxon
Polarizability39.6 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9927
Blood Brain Barrier+0.9731
Caco-2 permeable+0.8415
P-glycoprotein substrateSubstrate0.7911
P-glycoprotein inhibitor INon-inhibitor0.8385
P-glycoprotein inhibitor IINon-inhibitor0.9351
Renal organic cation transporterNon-inhibitor0.7774
CYP450 2C9 substrateNon-substrate0.8799
CYP450 2D6 substrateNon-substrate0.909
CYP450 3A4 substrateSubstrate0.7138
CYP450 1A2 substrateNon-inhibitor0.9306
CYP450 2C9 inhibitorNon-inhibitor0.9023
CYP450 2D6 inhibitorNon-inhibitor0.9201
CYP450 2C19 inhibitorNon-inhibitor0.9285
CYP450 3A4 inhibitorNon-inhibitor0.8772
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.903
Ames testNon AMES toxic0.8895
CarcinogenicityNon-carcinogens0.9479
BiodegradationNot ready biodegradable0.9964
Rat acute toxicity2.1686 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9591
hERG inhibition (predictor II)Inhibitor0.5213
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 21-hydroxysteroids. These are steroids carrying a hydroxyl group at the 21-position of the steroid backbone.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Hydroxysteroids
Direct Parent
21-hydroxysteroids
Alternative Parents
Gluco/mineralocorticoids, progestogins and derivatives / 20-oxosteroids / 11-beta-hydroxysteroids / 17-hydroxysteroids / 3-oxo delta-4-steroids / Halogenated steroids / Delta-4-steroids / Cyclohexenones / Tertiary alcohols / Alpha-hydroxy ketones
show 8 more
Substituents
Progestogin-skeleton / 21-hydroxysteroid / Pregnane-skeleton / 20-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / 17-hydroxysteroid / 11-hydroxysteroid / 11-beta-hydroxysteroid / 9-halo-steroid
show 24 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
11beta-hydroxy steroid, 17alpha-hydroxy steroid, 3-oxo Delta(4)-steroid, 20-oxo steroid, fluorinated steroid, mineralocorticoid, 21-hydroxy steroid, C21-steroid (CHEBI:50885) / C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C07004) / C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030103)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates targ...
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
Molecular Weight
107066.575 Da
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:12888122]
  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:8157723]
  3. Young MJ, Funder JW: Mineralocorticoids, salt, hypertension: effects on the heart. Steroids. 1996 Apr;61(4):233-5. [PubMed:8733007]
  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:12198239]
  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 Sep-Nov;32(8-10):859-64. Epub 2007 Jul 30. [PubMed:17666187]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Trune DR, Kempton JB: Low dose combination steroids control autoimmune mouse hearing loss. J Neuroimmunol. 2010 Dec 15;229(1-2):140-5. doi: 10.1016/j.jneuroim.2010.07.026. Epub 2010 Aug 30. [PubMed:20800906]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
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:11956172]
  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(ccr)) derived from an androgen-independent prostate cancer. J Med Chem. 2002 Mar 28;45(7):1439-46. [PubMed:11906285]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Vienna presentation 2012 [File]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:45