Fludrocortisone acetate Chemical Properties

Melting point:

233-234°C

alpha 

D23 +123° (c = 0.64 in chloroform)

Boiling point:

575.1±50.0 °C(Predicted)

Density 

1.0953 (rough estimate)

refractive index 

1.5980 (estimate)

storage temp. 

2-8°C

solubility 

Practically insoluble in water, sparingly soluble in anhydrous ethanol.

pka

12.06±0.70(Predicted)

color 

White to Off-White

Water Solubility 

54mg/L(25 ºC)

InChIKey

UUHYILPJUKGJDI-XYNXPQAZSA-N

SMILES

F[C@]12[C@H](C[C@@]3([C@@](O)(C(=O)COC(=O)C)CC[C@@]3([H])[C@]1([H])CCC1=CC(=O)CC[C@]21C)C)O |&1:1,2,4,5,16,18,28,r|

CAS DataBase Reference

514-36-3(CAS DataBase Reference)

EPA Substance Registry System

Fluorocortisone acetate (514-36-3)

Safety Information

Hazard Codes 

Xn

Risk Statements 

63

Safety Statements 

22-26-36

WGK Germany 

3

RTECS 

TU5050000

HS Code 

2937220000

Toxicity

LD50 oral in rat: > 1gm/kg

Fludrocortisone acetate Usage And Synthesis

Description

Fludrocortisone acetate is the acetate form of the synthetic corticosteroid fludrocortisone, which is a mineralocorticoid receptor agonist. Fludrocortisone acetate (0.1-5 μg/animal) promotes sodium retention in rats in a dose-dependent manner with 37% of sodium excreted compared with control when used at a dose of 5 μg/animal. Formulations containing fludrocortisone acetate have been used in the treatment of Addison’s disease.

Chemical Properties

Crystalline Solid

Originator

Alflorone Acetate,MSD,US,1954

Definition

ChEBI: An acetate ester resulting from the formal condensation of the primary hydroxy group of fludrocortisone with acetic acid. A synthetic corticosteroid, it has glucocorticoid actions about 10 times as potent as hydrocortisone, while its mineralocorticoid acti ns are over 100 times as potent. It is used in partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison's disease and for the treatment of salt-losing adrenal hyperplasia.

Manufacturing Process

Hydrocortisone acetate is first reacted with phosphorus oxychloride in pyridine to give the corresponding olefin. Then a sequence consisting of hypobromous acid addition, ring closure to the epoxide and ring opening with hydrogen fluoride gives fludrocortisone acetate. Preparation of a crystalline product is described then in US Patent 2,957,013.

brand name

Florinef (King).

Therapeutic Function

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

General Description

Fludrocortisone acetate,21-acetyloxy-9-fluoro-11β,17-dihydroxypregn-4-ene-3,20-dione, 9α-fluorohydrocortisone (Florinef Acetate), isused only for the treatment of Addison disease and for inhibitionof endogenous adrenocortical secretions. It has up to about 800 times the MC activity of hydrocortisone and about 11 times the GC activity. Its potent activity stimulated the synthesis and study of the many fluorinated steroids. Although its great salt-retaining activity limits its use to Addison disease, it has sufficient GC activity that in some cases of the disease, additional GCs need not be prescribed.

Biochem/physiol Actions

Fludrocortisone acetate is a synthetic corticosteroid with more mineralocorticoid than glucocorticoid activity.

Clinical Use

Fludrocortisone acetate is mineralocorticoid. It is used as a replacement therapy in adrenal insufficiency. 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. ludrocortisone is a man-made form of a natural substance (glucocorticoid) made by the body. It is used along with other medications (such as hydrocortisone) to treat low glucocorticoid levels caused by disease of the adrenal gland (such as Addison's disease, adrenocortical insufficiency, salt-losing adrenogenital syndrome). Glucocorticoids are needed in many ways for the body to function well. They are important for salt and water balance and keeping blood pressure normal. They are also needed to break down carbohydrates in your diet.

Veterinary Drugs and Treatments

Fludrocortisone is used in small animal medicine for the treatment of adrenocortical insufficiency (Addison’s disease). It can also be used as adjunctive therapy in hyperkalemia.
Additionally, in humans, fludrocortisone has been used in saltlosing, congenital adrenogenital syndrome and in patients with severe postural hypotension.

Drug interactions

Potentially hazardous interactions with other drugs
Aldesleukin: avoid concomitant use.
Antibacterials: metabolism accelerated by rifamycins; metabolism possibly inhibited by erythromycin; possibly reduce isoniazid concentration.
Anticoagulants: efficacy of coumarins and phenindione may be altered.
Antiepileptics: metabolism accelerated by carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone.
Antifungals: increased risk of hypokalaemia with amphotericin - avoid; metabolism possibly inhibited by itraconazole and ketoconazole.
Antivirals: concentration possibly increased by ritonavir.
Cobicistat: concentration of fludrocortisone increased.
Vaccines: high dose corticosteroids can impair immune response to vaccines - avoid concomitant use with live vaccines

Metabolism

Fludrocortisone is hydrolysed to produce the nonesterified alcohol. In human volunteers, excretion through urine was about 80%, and it was concluded that about 20% were excreted by a different route. It is likely that, as for the metabolism of other steroids, excretion into the bile is balanced by re-absorption in the intestine and some part is excreted with the faeces

Fludrocortisone acetate(514-36-3)Related Product Information

• CORTISONE
• Dimethyl sulfide
• Dimethyl fumarate
• Hydrocortisone acetate
• Dimethyl sulfate
• Vinyl acetate
• N,N-Dimethylformamide
• Dimethyl sulfoxide
• Fludrocortisone
• Sodium acetate
• Ethyl acetate
• ETHANE
• Dimethyl ether
• Cellulose acetate
• Ammonium acetate
• POLY(VINYL ACETATE)
• Hydrocortisone
• Dimethyl carbonate