FLUDROCORTISONE ACETATE

First approved in 1955

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H31FO6
Molecular Weight	422.487
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=SYWHXTATXSMDSB-GSLJADNHSA-N

InChI=1S/C23H31FO6/c1-13(25)30-12-19(28)22(29)9-7-16-17-5-4-14-10-15(26)6-8-20(14,2)23(17,24)18(27)11-21(16,22)3/h10,16-18,27,29H,4-9,11-12H2,1-3H3/t16-,17-,18-,20-,21-,22-,23-/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 2678	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 2678
Glucocorticoid receptor 172 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 2678
Glucocorticoid receptor 172 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 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Addison's disease 2 Sources: https://www.drugs.com/cdi/florinef.html	Primary		Approved 8429	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 8429	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 n = 5 Health Status: unhealthy Condition: anuric patients with symptomatic hypotension Population Size: 5 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 n = 5 Health Status: unhealthy Condition: anuric patients with symptomatic hypotension Population Size: 5 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 n = 5 Health Status: unhealthy Condition: anuric patients with symptomatic hypotension Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/12372940

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A 191

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A 191	substrate 3367 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
ZINC	ZINC000004097304	http://zinc15.docking.org/substances/ZINC000004097304
eMolecules	31226069	https://www.emolecules.com/cgi-bin/more?vid=31226069

PubMed

Title	Date	PubMed
The use of oral vasopressors in the management of autonomic dysfunction and orthostatic hypotension.	1999 May	10369619
Steroids in sepsis--more effective than activated protein C?	2001 Aug	11868733
[An autopsy case of pure autonomic failure with pathological features of Parkinson's disease].	2001 Jan	11433766
Adverse cardiac effects of salt with fludrocortisone in hypertension.	2001 Mar	11244008
Dysautonomia and neurocardiogenic syncope.	2001 Mar	11224639
Orthostatic hypotension and chronic fatigue syndrome.	2001 Mar 21	11255414
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
Outcomes for laparoscopic bilateral adrenalectomy.	2002 Aug	12269488
Chronic unexplained fatigue.	2002 Dec	12509703
[Syncope - a systematic overview of classification, pathogenesis, diagnosis and management].	2002 Feb	11823926
Corticosteroid supplementation for adrenal insufficiency.	2002 Jan 9	11779267
Autonomic failure mimicing dopamine agonist induced vertigo in a patient with macroprolactinoma.	2002 Oct	12397537
Sepsis clinical knowledge: a role of steroid treatment.	2003 Apr	12766716
Chronic fatigue syndrome and Addison's disease.	2003 Feb	12584556
Successful treatment of severe orthostatic hypotension with erythropoietin.	2003 Jan	12685148
Drug treatment of orthostatic hypotension and vasovagal syncope.	2003 Jan-Feb	12549988
Serum leptin levels in patients with 21-hydroxylase deficiency before and after treatment.	2003 Jan-Mar	12718369
Impact of smoking on the response to treatment of thyroid associated ophthalmopathy.	2003 Jun	12770979
Stability of fludrocortisone acetate solutions prepared from tablets and powder.	2003 Mar	12637099
Congenital adrenal hypoplasia presenting as a chronic respiratory condition.	2003 Mar	12598398

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

FLUDROCORTISONE ACETATE

Common Name

English

FLORINEF

Brand Name

English

FLUDROCORTISONE ACETATE [JAN]

Common Name

English

FLUDROCORTISONI ACETAS [WHO-IP LATIN]

Common Name

English

FLUDROCORTISONE ACETATE [USP-RS]

Common Name

English

FLUDROCORTISONE 21-ACETATE [MI]

Common Name

English

FLUDROCORTISONE ACETATE [EP MONOGRAPH]

Common Name

English

SCHEROFLURON

Common Name

English

NSC-15186

Code

English

FLUDROCORTISONE ACETATE [WHO-IP]

Common Name

English

9-Fluoro-11β,17,21-trihydroxypregn-4-ene-3,20-dione 21-acetate

Systematic Name

English

FLUOROCORTISOL ACETATE

Common Name

English

FLUDROCORTISONE ACETATE [USP MONOGRAPH]

Common Name

English

Fludrocortisone acetate [WHO-DD]

Common Name

English

FLUDROCORTISONE ACETATE [VANDF]

Common Name

English

FLUDROCORTISONE ACETATE [ORANGE BOOK]

Common Name

English

FLUDROCORTISONE ACETATE [MART.]

Common Name

English

PREGN-4-ENE-3,20-DIONE, 21-(ACETYLOXY)-9-FLUORO-11,17-DIHYDROXY-, (11.BETA.)-

Systematic Name

English

FLUDROCORTISONE 21-ACETATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C521