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
Association between supine hypertension and orthostatic hypotension in autonomic failure.	2003-08	12835329
Primary aldosteronism and hypertensive disease.	2003-08	12796282
Automated coupling of capillary-HPLC to matrix-assisted laser desorption/ionization mass spectrometry for the analysis of small molecules utilizing a reactive matrix.	2003-07	12802557
Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study.	2003-06-15	12829200
[A 47-year-old man with "pure autonomic failure" and pernicious anemia].	2003-06-13	12802744
Monozygotic twins with congenital adrenal hyperplasia: long-term endocrine evaluation and gene analysis.	2003-06-10	12793610
Neurologic complications following treatment of canine hypoadrenocorticism.	2003-06	12839244
Impact of smoking on the response to treatment of thyroid associated ophthalmopathy.	2003-06	12770979
Corticosteroid insufficiency in acutely ill patients.	2003-05-22	12765169
Hyperpigmentation mimicking Laugier syndrome, levodopa therapy and Addison's disease.	2003-05	12702077
Blood pressure in children and adolescents with congenital adrenal hyperplasia (21-hydroxylase deficiency): a preliminary report.	2003-05	12699440
Serum leptin levels in patients with 21-hydroxylase deficiency before and after treatment.	2003-04-30	12718369
Simultaneous quantification of budesonide and its two metabolites, 6beta-hydroxybudesonide and 16alpha-hydroxyprednisolone, in human plasma by liquid chromatography negative electrospray ionization tandem mass spectrometry.	2003-04-30	12717805
Sepsis clinical knowledge: a role of steroid treatment.	2003-04	12766716
Bench-to-bedside review: endothelial cell dysfunction in severe sepsis: a role in organ dysfunction?	2003-04	12720559
Diminished renal kallikrein responses to mineralocorticoid stimulation in African Americans: determinants of an intermediate phenotype for hypertension.	2003-04	12670744
Hydrocortisone and fludrocortisone improved 28-day survival in septic shock and adrenal insufficiency.	2003-03-05	12614129
Stability of fludrocortisone acetate solutions prepared from tablets and powder.	2003-03	12637099
Parkinsonism associated with Addison's disease.	2003-03	12621641
Granulomatous interstitial nephritis.	2003-03	12612999
Congenital adrenal hypoplasia presenting as a chronic respiratory condition.	2003-03	12598398
Recently published papers: a number of treatment controversies.	2003-02	12617735
Chronic fatigue syndrome and Addison's disease.	2003-02	12584556
Drug treatment of orthostatic hypotension and vasovagal syncope.	2003-01-29	12549988
Treating interdialytic hyperkalemia with fludrocortisone.	2003-01-22	12535291
Successful treatment of severe orthostatic hypotension with erythropoietin.	2003-01	12685148
[Investigation of hyperaldosteronism in the hypertensive patient. Why? When? How?].	2003-01	12613148
A pilot randomized trial of induced blood pressure elevation: effects on function and focal perfusion in acute and subacute stroke.	2003	12865611
Neurocardiogenic syncope in children : current concepts in diagnosis and management.	2003	12716219
Reducing mortality in sepsis: new directions.	2002-12	12720570
Chronic unexplained fatigue.	2002-12	12509703
Treatment of orthostatic hypotension.	2002-12	12482740
Dysautonomias: clinical disorders of the autonomic nervous system.	2002-11-05	12416949
[Generic carbamazepine-induced subacute adrenal insufficiency?].	2002-11	12598835
Screening and diagnosis of primary aldosteronism.	2002-10-22	12389057
[Diabetic neuropathy--concept, staging, diagnosis, treatment].	2002-10	12430228
Recently published papers: new evidence for old debates, new drugs and some timely reminders.	2002-10	12398779
Autonomic failure mimicing dopamine agonist induced vertigo in a patient with macroprolactinoma.	2002-10	12397537
Hyperaldosteronism: the internist's hypertensive disease.	2002-10	12385496
The mineralocorticoid receptor may compensate for the loss of the glucocorticoid receptor at specific stages of mammary gland development.	2002-09	12198239
Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.	2002-08-21	12186604
[Primary adrenal insufficiency due to autoimmune adrenalitis].	2002-08	12360800
Outcomes for laparoscopic bilateral adrenalectomy.	2002-08	12269488
Longitudinal analysis of growth and puberty in 21-hydroxylase deficiency patients.	2002-08	12138066
Salt losing nephropathy simulating congenital adrenal hyperplasia in an infant.	2002-07	12174243
A footnote on the origin of fluorosteroids.	2002-07	12077592
Yoghurt biotherapy: contraindicated in immunosuppressed patients?	2002-06	12151695
Cortisol replacement for severe sepsis and septic shock: what should I do?	2002-06	12133175
Orthostatic hypotension.	2002-05	12180246
Potassium-lowering effect of mineralocorticoid therapy in patients undergoing hemodialysis.	2002	12372940

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