Contact us: +91 9550333722 040 - 40102781
Structured search
India
Choose your country
Different countries will display different contents
Try our best to find the right business for you.
My chemicalbook

Welcome back!

HomeProduct name listFludrocortisone

Fludrocortisone

  • CAS NO.:127-31-1
  • Empirical Formula: C21H29FO5
  • Molecular Weight: 380.45
  • MDL number: MFCD00083333
  • EINECS: 204-833-2
  • SAFETY DATA SHEET (SDS)
  • Update Date: 2024-11-04 20:04:50
Fludrocortisone Structural

What is Fludrocortisone?

Absorption

Absorption of fludrocortisone following oral administration is rapid and complete. Pharmacokinetic studies have estimated the Cmax to be 0.0012 to 0.20 μg/L with a Tmax between 0.5 and 2 hours. The AUC0-∞ of fludrocortisone after oral administration has been variably estimated to be between 1.22 to 3.07 μg.h/L.

Toxicity

The oral LD50 of fludrocortisone in rats is >1g/kg. Acute overdosage of fludrocortisone is likely to result in symptoms consistent with its adverse effect profile. Patients receiving a single large dose should be treated with plenty of water by mouth and should undergo monitoring of serum electrolytes, particularly potassium and sodium, and be treated appropriately for any developing imbalances.

Chemical properties

White Solid

Originator

Alflorone Acetate,MSD,US,1954

The Uses of Fludrocortisone

A mineralocorticoid

The Uses of Fludrocortisone

A mineralocorticoid.

Indications

Fludrocortisone is indicated as partial replacement therapy for primary or secondary adrenocortical insufficiency in Addison's disease. It is also indicated for the treatment of salt-losing androgenital syndrome.

What are the applications of Application

Fludrocortisone is A mineralocorticoid

What are the applications of Application

Fludrocortisone-d5 is a labeled synthetic corticosteroid

Background

Fludrocortisone is a synthetic mineralocorticoid used in conjunction with hydrocortisone to replace missing endogenous corticosteroids in patients with adrenal insufficiency. It is functionally similar to aldosterone, the body's primary endogenous mineralocorticoid, and is structurally analogous to cortisol, differing only by a fluorine atom at the 9-position of the steroid structure - this fluorination is thought to be crucial to fludrocortisone's significant mineralocorticoid potency.

Definition

ChEBI: Fludrocortisone is a C21-steroid, a 3-oxo-Delta(4) steroid, a 20-oxo steroid, a 21-hydroxy steroid, a fluorinated steroid, a mineralocorticoid, a 17alpha-hydroxy steroid and an 11beta-hydroxy steroid. It has a role as an adrenergic agent and an anti-inflammatory drug. It derives from a hydride of a pregnane.

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

Pharmacokinetics

Fludrocortisone is a synthetic mineralocorticoid used to replace endogenous aldosterone in conditions resulting in missing or inadequate endogenous synthesis. It acts on the kidneys to increase both sodium reabsorption and potassium excretion. As its effects are exerted at the transcriptional level, a single dose of fludrocortisone may work over the course of 1-2 days despite a relatively short plasma half-life. Like other systemic corticosteroids, fludrocortisone may mask signs of infection by depressing the normal immune response - infections occurring during fludrocortisone therapy should be promptly treated with appropriate antimicrobial therapy.

Clinical Use

Fludrocortisone acetate is used orally for mineralocorticoid replacement therapy in patients with adrenocortical insufficiency, such as Addison's disease. This drug, introduced in 1954, helped to provide the impetus for the synthesis and biological evaluation of newer halogenated analogues.

Synthesis

Fludrocortisone, 9|á-fluoro-11|?,17|á,21-trihydroxypregn-4-en-3,20- dione (27.2.14), is synthesized from hydrocortisone acetate (27.1.17). In the first stage of synthesis, dehydration of the hydrocortisone molecules is accomplished using phosphorous chloride in pyridine, which forms a product with a double bond at C9¨CC11 27.2.11. The resulting double bond is synthesized into an epoxide by an initial transformation to a bromohydrine using N-bromoacetamide and subsequent dehydrobromination using sodium acetate, which forms 21-O-acetoxy-9d-11|?-epoxy-17|á-hydroxy-4-pregnen-3,20-dione (27.2.12). As described above, the epoxide ring is opened by hydrofluoric acid, which results in the formation of the 21-O-acetate of fludrocortisone 27.2.13. Hydrolysis of the acetyl group of this compound using potassium acetate gives fludrocortisone (27.2.14).

Synthesis_127-31-1

Metabolism

There exists is a paucity of information regarding the specific metabolic pathway in vivo of fludrocortisone. The 9α-fluorination of fludrocortisone appears to greatly simplify its metabolism as compared to other corticosteroids - while oxidation via 11-hydroxysteroid dehydrogenases has been observed, this reaction is greatly impaired as the fluorine moiety appears to confer "protection" from 11β-oxidation by these enzymes. The reduction in 11β-oxidation is thought to be one of the reasons behind fludrocortisone's profound mineralocorticoid potency. An in vitro study generated only two metabolites following incubation in human liver microsomes and cytosol, namely 20β-dihydrofluorocortisol and 6β-hydroxyfluorocortisol, and did not explore in detail the potential enzymes responsible for this reaction.
Given that fludrocortisone is a corticosteroid, a class of medications known to be metabolized by the CYP3A family, and is not recommended to be given with strong inhibitors/inducers of CYP3A, it is likely that the CYP3A family of enzymes contributes in some way to its metabolism (though this information does not appear to have been specifically elucidated for fludrocortisone).

Properties of Fludrocortisone

Melting point: 208-212°C
Boiling point: 564.7±50.0 °C(Predicted)
alpha  D23 +139° (c = 0.55 in 95% ethanol)
Density  1.1176 (estimate)
storage temp.  Refrigerator
solubility  DMSO (Slightly), Ethanol (Slightly, Heated), Methanol (Slightly, Sonicated)
form  Solid
pka 12.11±0.70(Predicted)
color  White to Off-White
Water Solubility  111mg/L(25 ºC)
CAS DataBase Reference 127-31-1(CAS DataBase Reference)
EPA Substance Registry System Hydrocortisone-9.alpha.-fluoro (127-31-1)

Safety information for Fludrocortisone

Computed Descriptors for Fludrocortisone

Related products of tetrahydrofuran

You may like

Statement: All products displayed on this website are only used for non medical purposes such as industrial applications or scientific research, and cannot be used for clinical diagnosis or treatment of humans or animals. They are not medicinal or edible.