FLUDROCORTISONE

First approved in 1955

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H29FO5
Molecular Weight	380.4504
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=AAXVEMMRQDVLJB-BULBTXNYSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.medsafe.govt.nz/profs/datasheet/f/Florineftab.pdf
Curator's Comment: description was created based on several sources, including http://www.2ndchance.info/addison's-florinef.pdf

Fludrocortisone acetate (approved as Florinef) is a synthetic adrenocortical steroid possessing very potent mineralcorticoid properties and high glucocorticoid activity. Main indications are Partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison's disease and for the treatment of salt losing adrenogenital syndrome.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Mineralocorticoid receptor 53 Target ID: P22199 Gene ID: 25672.0 Gene Symbol: Nr3c2 Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/611629	Agonist 2752	1.07 nM [Kd]
Mineralocorticoid receptor 53 Target ID: P08235 Gene ID: 4306.0 Gene Symbol: NR3C2 Target Organism: Homo sapiens (Human) Sources: http://www.genome.jp/kegg-bin/show_pathway?map07225+D00986	Agonist 2752
Glucocorticoid receptor 173 Target ID: P06536 Gene ID: 24413.0 Gene Symbol: Nr3c1 Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/611629	Agonist 2752
Glucocorticoid receptor 173 Target ID: P04150 Gene ID: 2908.0 Gene Symbol: NR3C1 Target Organism: Homo sapiens (Human) Sources: http://www.genome.jp/kegg-bin/show_pathway?map07225+D00986	Agonist 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Addison's disease 2 Sources: https://www.drugs.com/cdi/florinef.html	Primary		Approved 8583	FLORINEF Approved Use Fludrocortisone acetate tablets USP, 0.1 mg are indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison's disease and for the treatment of salt-losing adrenogenital syndrome. Launch Date 1955
Salt-losing adrenogenital syndrome 2 Sources: https://www.drugs.com/cdi/florinef.html	Primary		Approved 8583	FLORINEF Approved Use Fludrocortisone acetate tablets USP, 0.1 mg are indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison's disease and for the treatment of salt-losing adrenogenital syndrome. Launch Date 1955

C_max

Value	Dose	Co-administered	Analyte	Population
1241.1 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25611194	0.1 mg single, oral dose: 0.1 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUDROCORTISONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.19 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27416887	50 μg single, oral dose: 50 μg route of administration: Oral experiment type: SINGLE co-administered:		FLUDROCORTISONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3275.8 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25611194	0.1 mg single, oral dose: 0.1 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUDROCORTISONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.25 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27416887	50 μg single, oral dose: 50 μg route of administration: Oral experiment type: SINGLE co-administered:		FLUDROCORTISONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25611194	0.1 mg single, oral dose: 0.1 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUDROCORTISONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.35 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27416887	50 μg single, oral dose: 50 μg route of administration: Oral experiment type: SINGLE co-administered:		FLUDROCORTISONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
30% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25611194	0.1 mg single, oral dose: 0.1 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUDROCORTISONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
0.3 mg 1 times / day multiple, oral Highest studied dose Dose: 0.3 mg, 1 times / day Route: oral Route: multiple Dose: 0.3 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12372940	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/12372940	Other AEs: Serum potassium decreased, Rise in blood pressure... Other AEs: Serum potassium decreased (5 patients) Rise in blood pressure (5 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/12372940

AEs

AE	Significance	Dose	Population
Rise in blood pressure	5 patients	0.3 mg 1 times / day multiple, oral Highest studied dose Dose: 0.3 mg, 1 times / day Route: oral Route: multiple Dose: 0.3 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12372940	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/12372940
Serum potassium decreased	5 patients	0.3 mg 1 times / day multiple, oral Highest studied dose Dose: 0.3 mg, 1 times / day Route: oral Route: multiple Dose: 0.3 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12372940	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/12372940

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A 220

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A 220	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/Fludrocortisone#section=Metabolism-Metabolites	likely

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:50885	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50885
ChemicalBook	CB7170706	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7170706
eMolecules	31226069	https://www.emolecules.com/cgi-bin/more?vid=31226069
ZINC	ZINC000004097304	http://zinc15.docking.org/substances/ZINC000004097304

PubMed

Title	Date	PubMed
Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone.	2000 Oct	11198485
[Addisonian myopathy].	2001	11596401
Hypoadrenocorticism in a cat.	2001 Apr	11327666
Steroids in sepsis--more effective than activated protein C?	2001 Aug	11868733
Mechanisms underlying the impairment in orthostatic tolerance after nocturnal recumbency in patients with autonomic failure.	2001 Dec	11724647
Endothelial cell dysfunction in mice after transgenic knockout of type 2, but not type 1, 11beta-hydroxysteroid dehydrogenase.	2001 Dec 4	11733403
[An autopsy case of pure autonomic failure with pathological features of Parkinson's disease].	2001 Jan	11433766
Aldosterone synthase deficiency type I with no documented homozygous mutations in the CYP11B2 gene.	2001 Jan	11174838
Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial.	2001 Jan 3	11150109
[Orthostatic intolerance syndromes].	2001 Jan-Mar	11565347
Dysautonomia and neurocardiogenic syncope.	2001 Mar	11224639
Orthostatic hypotension and chronic fatigue syndrome.	2001 Mar 21	11255416
Orthostatic hypotension and chronic fatigue syndrome.	2001 Mar 21	11255414
Insulin and mineralocorticoids influence on extrarenal potassium metabolism in chronic hemodialysis patients.	2001 Nov	11777323
Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene.	2001 Nov	11701710
[Adrenal insufficiency caused by treatment with levothyroxine].	2001 Nov 29	11770254
[Increasing pigmentation in Schmidt syndrome (polyglandular autoimmune syndrome type II].	2001 Oct	11715397
Fludrocortisone treatment in a child with severe cerebral salt wasting.	2001 Oct	11694800
Adverse cardiac effects of salt with fludrocortisone in hypertension.	2001 Oct	11641323
Pharmacologic options available to treat symptomatic intradialytic hypotension.	2001 Oct	11602458
Serum cortisol and 17-hydroxyprogesterone interrelation in classic 21-hydroxylase deficiency: is current replacement therapy satisfactory?	2001 Oct	11600525
Pro/con clinical debate: are steroids useful in the management of patients with septic shock?	2002 Apr	11983034
Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.	2002 Aug 21	12186604
Hyperkalaemia and selective hypoaldosteronism in myotonic dystrophy.	2002 Feb	11874420
The aldosterone-renin ratio and primary aldosteronism.	2002 Feb	11838659
[Syncope - a systematic overview of classification, pathogenesis, diagnosis and management].	2002 Feb	11823926
Hyporeninemic hypoaldosteronism associated with Sjögren's syndrome.	2002 Feb 15	11893359
Corticosteroid supplementation for adrenal insufficiency.	2002 Jan 9	11779267
A footnote on the origin of fluorosteroids.	2002 Jul	12077592
Screening and diagnosis of primary aldosteronism.	2002 Jul-Aug	12389057
Structural basis for the glucocorticoid response in a mutant human androgen receptor (AR(ccr)) derived from an androgen-independent prostate cancer.	2002 Mar 28	11906285
Dysautonomias: clinical disorders of the autonomic nervous system.	2002 Nov 5	12416949
The mineralocorticoid receptor may compensate for the loss of the glucocorticoid receptor at specific stages of mammary gland development.	2002 Sep	12198239
A pilot randomized trial of induced blood pressure elevation: effects on function and focal perfusion in acute and subacute stroke.	2003	12865611
Sepsis clinical knowledge: a role of steroid treatment.	2003 Apr	12766716
Bench-to-bedside review: endothelial cell dysfunction in severe sepsis: a role in organ dysfunction?	2003 Apr	12720559
Diminished renal kallikrein responses to mineralocorticoid stimulation in African Americans: determinants of an intermediate phenotype for hypertension.	2003 Apr	12670744
Monozygotic twins with congenital adrenal hyperplasia: long-term endocrine evaluation and gene analysis.	2003 Apr-May	12793610
Association between supine hypertension and orthostatic hypotension in autonomic failure.	2003 Aug	12835329
Primary aldosteronism and hypertensive disease.	2003 Aug	12796282
Chronic fatigue syndrome and Addison's disease.	2003 Feb	12584556
Successful treatment of severe orthostatic hypotension with erythropoietin.	2003 Jan	12685148
Serum leptin levels in patients with 21-hydroxylase deficiency before and after treatment.	2003 Jan-Mar	12718369
Automated coupling of capillary-HPLC to matrix-assisted laser desorption/ionization mass spectrometry for the analysis of small molecules utilizing a reactive matrix.	2003 Jul	12802557
Neurologic complications following treatment of canine hypoadrenocorticism.	2003 Jun	12839244
Impact of smoking on the response to treatment of thyroid associated ophthalmopathy.	2003 Jun	12770979
[A 47-year-old man with "pure autonomic failure" and pernicious anemia].	2003 Jun 13	12802744
Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study.	2003 Jun 15	12829200
Stability of fludrocortisone acetate solutions prepared from tablets and powder.	2003 Mar	12637099
Blood pressure in children and adolescents with congenital adrenal hyperplasia (21-hydroxylase deficiency): a preliminary report.	2003 May	12699440

Patents

Sample Use Guides

In Vivo Use Guide

0.05mg to 0.3mg FLORINEF (Fludrocortisone acetate) daily (depends on indication)

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

ASTONIN-H

Preferred Name

English

FLUDROCORTISONE

Official Name

English

fludrocortisone [INN]

Common Name

English

FLUDROCORTISONE [HSDB]

Common Name

English

FLUDROCORTISONE [VANDF]

Common Name

English

9-FLUORO-11.BETA.,17,21-TRIHYDROXYPREGN-4-ENE-3,20-DIONE

Systematic Name

English

NSC-11318

Code

English

FLUDROCORTISONE [MI]

Common Name

English

Fludrocortisone [WHO-DD]

Common Name

English

ALFLORONE

Brand Name

English

Classification Tree Code System Code

WHO-ATC

S03CA05