Identification

Name
Flurandrenolide
Accession Number
DB00846  (APRD00982)
Type
Small Molecule
Groups
Approved
Description

A corticosteroid used topically in the treatment of various skin disorders. It is usually employed as a cream or an ointment, and is also used as a polyethylene tape with an adhesive. (From Martindale, The Extra Pharmacopoeia, 30th ed, p733)

Structure
Thumb
Synonyms
  • Fludroxicortida
  • Fludroxicortide
  • Fludroxycortid
  • Fludroxycortide
  • Fludroxycortidum
  • Flurandrenolone
External IDs
33379 / Lilly 33379
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CordranCream0.5 mg/1gTopicalAqua Pharmaceuticals1965-10-18Not applicableUs
CordranCream0.5 mg/1gTopicalWatson Pharma, Inc.1965-10-182011-08-30Us
CordranLotion0.5 mg/1mLTopicalAqua Pharmaceuticals1963-03-19Not applicableUs
CordranTape4 ug/1cm2TopicalActavis Pharma Company1969-07-292018-07-10Us
CordranOintment0.5 mg/1gTopicalAqua Pharmaceuticals1965-10-18Not applicableUs
CordranOintment0.5 mg/1gTopicalWatson Pharma, Inc.1965-10-182011-08-30Us
CordranOintment0.25 mg/1gTopicalAqua Pharmaceuticals, LLC.2007-05-312007-05-31Us
CordranTape4 ug/1cm2TopicalWatson Labs1969-07-292010-11-17Us
CordranLotion0.5 mg/1mLTopicalPhysicians Total Care, Inc.1994-03-232010-06-30Us
CordranCream0.25 mg/1gTopicalWatson Pharma, Inc.1965-10-182011-08-30Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FlurandrenolideCream0.5 mg/1gTopicalTeligent Pharma, Inc.2016-04-132016-04-20Us
FlurandrenolideLotion0.5 mg/1mLTopicalCintex Services, Llc2016-12-22Not applicableUs
FlurandrenolideOintment0.5 mg/1gTopicalTeligent Pharma, Inc.2016-12-30Not applicableUs
FlurandrenolideLotion0.5 mg/1mLTopicalPerrigo New York Inc2016-10-06Not applicableUs
Flurandrenolide CreamCream0.5 mg/1gTopicalCintex Services, Llc2016-04-18Not applicableUs
NolixCream0.5 mg/1gTopicalArtesa Labs, Llc2018-01-26Not applicableUs
NolixLotion0.5 mg/1mLTopicalArtesa Labs, Llc2017-05-22Not applicableUs
International/Other Brands
Cordran / Cordran SP (Watson) / Drenison (Biolab) / Haelan (Typharm Limited)
Categories
UNII
8EUL29XUQT
CAS number
1524-88-5
Weight
Average: 436.5136
Monoisotopic: 436.226116993
Chemical Formula
C24H33FO6
InChI Key
POPFMWWJOGLOIF-XWCQMRHXSA-N
InChI
InChI=1S/C24H33FO6/c1-21(2)30-19-9-14-13-8-16(25)15-7-12(27)5-6-22(15,3)20(13)17(28)10-23(14,4)24(19,31-21)18(29)11-26/h7,13-14,16-17,19-20,26,28H,5-6,8-11H2,1-4H3/t13-,14-,16-,17-,19+,20+,22-,23-,24+/m0/s1
IUPAC Name
(1S,2S,4R,8S,9S,11S,12S,13R,19S)-19-fluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-17-en-16-one
SMILES
CC1(C)O[C@@H]2C[C@H]3[C@@H]4C[C@H](F)C5=CC(=O)CC[C@]5(C)[C@H]4[C@@H](O)C[C@]3(C)[C@@]2(O1)C(=O)CO

Pharmacology

Indication

For relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, particularly dry, scaling localized lesions

Associated Conditions
Pharmacodynamics

Flurandrenolide is primarily effective because of its anti-inflammatory, antipruritic, and vasoconstrictive actions.

Mechanism of action

Flurandrenolide is a topical corticosteroid. It is normally applied to a plastic tape called Cordran. Cordran is primarily effective because of its anti-inflammatory, antipruritic, and vasoconstrictive actions. Flurandrenolide, which is slowly released from the Cordran tape, binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. Cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Like other glucocorticoid agents Fluocinolone acetonide acts as a physiological antagonist to insulin by decreasing glycogenesis (formation of glycogen). It also promotes the breakdown of lipids (lipolysis), and proteins, leading to the mobilization of extrahepatic amino acids and ketone bodies. This leads to increased circulating glucose concentrations (in the blood). There is also decreased glycogen formation in the liver.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
Absorption

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to those of systemically administered corticosteroids

Volume of distribution
Not Available
Protein binding

Corticosteroids are bound to plasma proteins in varying degrees.

Metabolism

Primarily hepatic

Route of elimination

Topical corticosteroids can be absorbed from normal intact skin. They are metabolized primarily in the liver and then excreted in the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

Half life
Not Available
Clearance
Not Available
Toxicity

Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary- adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Casas-Campillo, C.; U.S. Patent 3,119,748; January 28, 1964; assigned to Syntex Corporation, Panama. Ringold, H.J., Zderic, J.A., Djerassi, C. and Bowers, A.; U.S. Patent 3,126,375; March 24, 1964; assigned to Syntex Corporation, Panama.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014984
KEGG Drug
D00328
PubChem Compound
15209
PubChem Substance
46505159
ChemSpider
14475
ChEBI
5127
ChEMBL
CHEMBL1201012
Therapeutic Targets Database
DAP000418
PharmGKB
PA164750513
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Fludroxycortide
ATC Codes
D07AC07 — FludroxycortideD07CC03 — Fludroxycortide and antibiotics
AHFS Codes
  • 84:06.00 — Anti-inflammatory Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2TerminatedTreatmentAnorexic / Cachexia / Obese experiencing rapid weight loss1

Pharmacoeconomics

Manufacturers
  • Watson pharmaceuticals inc
  • Watson laboratories inc
  • Alpharma us pharmaceuticals division
Packagers
  • Aqua Pharmaceuticals
  • DPT Laboratories Ltd.
  • Oclassen Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
CreamTopical0.5 mg/1g
LotionTopical0.5 mg/1mL
OintmentTopical0.25 mg/1g
OintmentTopical0.5 mg/1g
TapeTopical4 ug/1cm2
CreamTopical0.25 mg/1g
TapeTopical4 mcg
Prices
Unit descriptionCostUnit
Cordran (80 X 3 Inch) Box Box105.02USD box
Cordran 4 mcg/sqcm Tape (24 X 3 Inch) Box53.63USD box
Cordran 0.05% lotion4.8USD ml
Cordran sp 0.05% cream4.8USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)251 °CPhysProp
water solubilityInsolubleNot Available
logP0.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0578 mg/mLALOGPS
logP2.02ALOGPS
logP1.56ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)13.74ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area93.06 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity110.79 m3·mol-1ChemAxon
Polarizability45.51 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9796
Blood Brain Barrier+0.9739
Caco-2 permeable+0.5279
P-glycoprotein substrateSubstrate0.8046
P-glycoprotein inhibitor INon-inhibitor0.6488
P-glycoprotein inhibitor IINon-inhibitor0.7127
Renal organic cation transporterNon-inhibitor0.7839
CYP450 2C9 substrateNon-substrate0.862
CYP450 2D6 substrateNon-substrate0.8911
CYP450 3A4 substrateSubstrate0.7258
CYP450 1A2 substrateNon-inhibitor0.9294
CYP450 2C9 inhibitorNon-inhibitor0.9269
CYP450 2D6 inhibitorNon-inhibitor0.9481
CYP450 2C19 inhibitorNon-inhibitor0.9398
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9098
Ames testNon AMES toxic0.8398
CarcinogenicityNon-carcinogens0.934
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2002 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9652
hERG inhibition (predictor II)Non-inhibitor0.5679
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001s-3961000000-a326b0165af296ecf245

Taxonomy

Description
This compound belongs to the class of organic compounds known as 21-hydroxysteroids. These are steroids carrying a hydroxyl group at the 21-position of the steroid backbone.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Hydroxysteroids
Direct Parent
21-hydroxysteroids
Alternative Parents
Gluco/mineralocorticoids, progestogins and derivatives / 20-oxosteroids / 11-beta-hydroxysteroids / 3-oxo delta-4-steroids / Halogenated steroids / Delta-4-steroids / Ketals / Cyclohexenones / 1,3-dioxolanes / Alpha-hydroxy ketones
show 8 more
Substituents
Progestogin-skeleton / 21-hydroxysteroid / Pregnane-skeleton / 20-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / 6-halo-steroid / Halo-steroid / 11-hydroxysteroid / 11-beta-hydroxysteroid
show 25 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Baschant U, Tuckermann J: The role of the glucocorticoid receptor in inflammation and immunity. J Steroid Biochem Mol Biol. 2010 May 31;120(2-3):69-75. doi: 10.1016/j.jsbmb.2010.03.058. Epub 2010 Mar 24. [PubMed:20346397]
  2. Fitzgerald P, O'Brien SM, Scully P, Rijkers K, Scott LV, Dinan TG: Cutaneous glucocorticoid receptor sensitivity and pro-inflammatory cytokine levels in antidepressant-resistant depression. Psychol Med. 2006 Jan;36(1):37-43. Epub 2005 Oct 28. [PubMed:16255837]
  3. Issar M, Sahasranaman S, Buchwald P, Hochhaus G: Differences in the glucocorticoid to progesterone receptor selectivity of inhaled glucocorticoids. Eur Respir J. 2006 Mar;27(3):511-6. [PubMed:16507850]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. NCI/NIH [Link]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Steroid binding
Specific Function
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
Gene Name
SERPINA6
Uniprot ID
P08185
Uniprot Name
Corticosteroid-binding globulin
Molecular Weight
45140.49 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Emptoz-Bonneton A, Cousin P, Seguchi K, Avvakumov GV, Bully C, Hammond GL, Pugeat M: Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity. J Clin Endocrinol Metab. 2000 Jan;85(1):361-7. [PubMed:10634411]
  4. Smith CL, Power SG, Hammond GL: A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol. J Steroid Biochem Mol Biol. 1992 Aug;42(7):671-6. [PubMed:1504007]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 12, 2018 07:23