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Identification
NameFludrocortisone
Accession NumberDB00687  (APRD00756, DB02478)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
Synonyms
SynonymLanguageCode
9alpha-FLUOROCORTISOLNot AvailableNot Available
FludrocortisonGermanINN
FludrocortisonaSpanishINN
FludrocortisoneFrenchINN
FludrocortisonumLatinINN
FluohydrocortisoneNot AvailableIS
Salts
Name/CAS Structure Properties
Fludrocortisone Acetate
Thumb
  • InChI Key: SYWHXTATXSMDSB-GSLJADNHSA-N
  • Monoisotopic Mass: 422.210466929
  • Average Mass: 422.487
DBSALT000659
Brand names
NameCompany
AdixoneGenopharm
AstoninMerck
CortineffPolfa Pabianice
Florinef AcetaatBristol-Myers Squibb
FlorinefeBristol-Myers Squibb
FludrocortisonBristol-Myers Squibb
LonikanMerck
Brand mixtures
Brand NameIngredients
NeoproctFludrocortisone and Lidocaine
Categories
CAS number127-31-1
WeightAverage: 380.4504
Monoisotopic: 380.199902243
Chemical FormulaC21H29FO5
InChI KeyAAXVEMMRQDVLJB-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[8.7.0.0^{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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassGluco/mineralocorticoids, Progestogins and Derivatives
Direct parentGluco/mineralocorticoids, Progestogins and Derivatives
Alternative parentsHydroxysteroids; Halogenated Steroids; Ketosteroids; Cyclohexanols; Tertiary Alcohols; Ketones; Cyclic Alcohols and Derivatives; Fluorohydrins; Enolates; Polyamines; Primary Alcohols; Organofluorides; Alkyl Fluorides; Aldehydes
Substituents20-keto-steroid; 11-hydroxy-steroid; 9-halo-steroid; 17-hydroxy-steroid; 3-keto-steroid; cyclohexanol; cyclic alcohol; tertiary alcohol; secondary alcohol; ketone; fluorohydrin; halohydrin; enolate; primary alcohol; polyamine; organofluoride; organohalogen; alcohol; carbonyl group; alkyl halide; alkyl fluoride; aldehyde
Classification descriptionThis compound belongs to the gluco/mineralocorticoids, progestogins and derivatives. These are steroids whose structure is based on an hydroxylated prostane moiety.
Pharmacology
IndicationFor partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison's disease and for the treatment of salt-losing adrenogenital syndrome.
PharmacodynamicsFludrocortisone 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 actionFludrocortisone 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingHigh
Metabolism

Hepatic, some renal.

Route of eliminationNot Available
Half life3.5 hours
ClearanceNot Available
ToxicityEffects 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9927
Blood Brain Barrier + 0.9731
Caco-2 permeable + 0.8415
P-glycoprotein substrate Substrate 0.7911
P-glycoprotein inhibitor I Non-inhibitor 0.8385
P-glycoprotein inhibitor II Non-inhibitor 0.9351
Renal organic cation transporter Non-inhibitor 0.7774
CYP450 2C9 substrate Non-substrate 0.8799
CYP450 2D6 substrate Non-substrate 0.909
CYP450 3A4 substrate Substrate 0.7138
CYP450 1A2 substrate Non-inhibitor 0.9306
CYP450 2C9 substrate Non-inhibitor 0.9023
CYP450 2D6 substrate Non-inhibitor 0.9201
CYP450 2C19 substrate Non-inhibitor 0.9285
CYP450 3A4 substrate Non-inhibitor 0.8772
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.903
Ames test Non AMES toxic 0.8895
Carcinogenicity Non-carcinogens 0.9479
Biodegradation Not ready biodegradable 0.9964
Rat acute toxicity 2.1686 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9591
hERG inhibition (predictor II) Inhibitor 0.5213
Pharmacoeconomics
Manufacturers
  • King pharmaceuticals inc
  • Barr laboratories inc
  • Impax laboratories inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Fludrocortisone acetate powder73.14USDg
Florinef acetate 0.1 mg tablet1.49USDtablet
Fludrocortisone Acetate 0.1 mg tablet0.81USDtablet
Fludrocortisone 0.1 mg tablet0.75USDtablet
Florinef 0.1 mg Tablet0.25USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
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 Solubility0.224ALOGPS
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
Spectra
SpectraNot Available
References
Synthesis Reference

U.S. Patent 2,957,013

General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07004
PubChem Compound31378
PubChem Substance46508616
ChemSpider29111
ChEBI50885
ChEMBLCHEMBL1201388
Therapeutic Targets DatabaseDAP001105
PharmGKBPA164743961
IUPHAR2873
Guide to Pharmacology2873
Drug Product Database2086026
RxListhttp://www.rxlist.com/cgi/generic/fludro.htm
Drugs.comhttp://www.drugs.com/cdi/fludrocortisone.html
WikipediaFludrocortisone
ATC CodesH02AA02
AHFS Codes
  • 68:04.00
PDB Entries
FDA labelNot Available
MSDSshow(73 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolThe corticosteroid, fludrocortisone, alters the anticoagulant effect, acenocoumarol.
Acetylsalicylic acidThe corticosteroid, fludrocortisone, may decrease the effect of the salicylate, acetylsalicylic acid.
AmbenoniumThe corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, ambenonium.
AmobarbitalThe barbiturate, amobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
AnisindioneThe corticosteroid, fludrocortisone, alters the anticoagulant effect of anisindione.
AprobarbitalThe barbiturate, aprobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Bismuth SubsalicylateThe corticosteroid, fludrocortisone, may decrease the effect of the salicylate, bismuth subsalicylate.
ButabarbitalThe barbiturate, butabarbital, may decrease the effect of the corticosteroid, fludrocortisone.
ButalbitalThe barbiturate, butalbital, may decrease the effect of the corticosteroid, fludrocortisone.
ButethalThe barbiturate, butethal, may decrease the effect of the corticosteroid, fludrocortisone.
DicoumarolThe corticosteroid, fludrocortisone, alters the anticoagulant effect of dicumarol.
Dihydroquinidine barbiturateThe barbiturate, dihydroquinidine barbiturate, may decrease the effect of the corticosteroid, fludrocortisone.
EdrophoniumThe corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, edrophonium.
EthotoinThe enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, fludrocortisone.
FosphenytoinThe enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, fludrocortisone.
HeptabarbitalThe barbiturate, heptabarbital, may decrease the effect of the corticosteroid, fludrocortisone.
HexobarbitalThe barbiturate, hexobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Magnesium salicylateThe corticosteroid, fludrocortisone, may decrease the effect of magnesium salicylate.
MephenytoinThe enzyme inducer, mephenytoin, may decrease the effect of the corticosteroid, fludrocortisone.
MethohexitalThe barbiturate, methohexital, may decrease the effect of the corticosteroid, fludrocortisone.
MethylphenobarbitalThe barbiturate, methylphenobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
MidodrineIncreased arterial pressure
NeostigmineThe corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, neostigmine.
PentobarbitalThe barbiturate, pentobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
PhenobarbitalThe barbiturate, phenobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
PhenytoinThe enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, fludrocortisone.
PrimidoneThe barbiturate, primidone, may decrease the effect of the corticosteroid, fludrocortisone.
PyridostigmineThe corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, pyridostigmine.
Quinidine barbiturateThe barbiturate, quinidine barbiturate, may decrease the effect of the corticosteroid, fludrocortisone.
RifampicinThe enzyme inducer, rifampin, may decrease the effect of the corticosteroid, fludrocortisone.
Salicylate-sodiumThe corticosteroid, fludrocortisone, may decrease the effect of the salicylate, salicylate-sodium.
SalsalateThe corticosteroid, fludrocortisone, may decrease the effect of the salicylate, salsalate.
SecobarbitalThe barbiturate, secobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
TacrineTacrine and Fludrocortisone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
TalbutalThe barbiturate, talbutal, may decrease the effect of the corticosteroid, fludrocortisone.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Trisalicylate-cholineThe corticosteroid, fludrocortisone, may decrease the effect of the salicylate, trisalicylate-choline.
VecuroniumVecuronium may increase the adverse neuromuscular effects of systemic corticosteroids, such as Fludrocortisone. Monitor for increased muscle weakness and signs of polyneuropathies and myopathy.
WarfarinThe corticosteroid, fludrocortisone, alters the anticoagulant effect of warfarin.
Food Interactions
  • Avoid excess salt/sodium unless otherwise instructed by your physician.
  • Take with food to reduce irritation.

Targets

1. Mineralocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Mineralocorticoid receptor P08235 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Glucocorticoid receptor P04150 Details

References:

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

3. Androgen receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Androgen receptor P10275 Details

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

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Drug created on June 13, 2005 07:24 / Updated on April 23, 2014 15:05