Identification

Name
Fluorometholone
Accession Number
DB00324  (APRD00980)
Type
Small Molecule
Groups
Approved, Investigational
Description

A glucocorticoid employed, usually as eye drops, in the treatment of allergic and inflammatory conditions of the eye. It has also been used topically in the treatment of various skin disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p732)

Structure
Thumb
Synonyms
  • (1R,2S,8S,10S,11S,14R,15S,17S)-14-acetyl-1-fluoro-14,17-dihydroxy-2,8,15-trimethyltetracyclo[8.7.0.02,7.011,15]heptadeca-3,6-dien-5-one
  • 9-Fluoro-11beta,17-dihydroxy-6alpha-methylpregna-1,4-diene-3,20-dione
  • Fluorometholon
  • Fluorométholone
  • Fluorometholone
  • Fluorometholonum
  • Fluorometolona
  • NSC 33001
  • Oxylone
External IDs
U 17323
Product Ingredients
IngredientUNIICASInChI Key
Fluorometholone acetate9I50C3I3OK3801-06-7YRFXGQHBPBMFHW-SBTZIJSASA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FlarexSuspension0.1 %OphthalmicNovartis1987-12-31Not applicableCanada
FlarexSuspension / drops1 mg/1mLOphthalmicALCON LABORATORIES, INC.1992-02-06Not applicableUs
Fluor-OpSuspension0.1 mL/100mLOphthalmicNovartis Ophthalmics2006-05-11Not applicableUs
FMLSuspension / drops1 mg/1mLOphthalmicAllergan1972-02-01Not applicableUs
FMLSuspension / drops1 mg/1mLOphthalmicA-S Medication Solutions1972-02-012017-04-30Us
FMLOintment1 mg/1gOphthalmicAllergan1985-12-09Not applicableUs
FML 0.1%Solution / drops0.1 %OphthalmicAllergan1972-12-31Not applicableCanada
FML ForteSuspension / drops2.5 mg/1mLOphthalmicAllergan1986-05-01Not applicableUs
FML Forte Sus 0.25%Suspension0.25 %OphthalmicAllergan1987-12-312016-04-06Canada
Sandoz FluorometholoneSuspension0.1 %OphthalmicSandoz Canada Incorporated2012-07-24Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FluorometholoneSolution / drops1 mg/1mLOphthalmicPacific Pharma1997-10-31Not applicableUs
PMS-fluorometholoneSuspension0.1 %OphthalmicPharmascience Inc2001-07-162016-10-28Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
FML-neo Oph SusFluorometholone (0.1 %) + Neomycin sulfate (0.5 %)SuspensionOphthalmicAllergan1977-12-312011-08-04Canada
FML-SFluorometholone (1.0 mg/1mL) + Sulfacetamide sodium (100 mg/1mL)SuspensionOphthalmicAllergan2007-02-20Not applicableUs
TobraflexFluorometholone acetate (1 mg/1mL) + Tobramycin (3 mg/1mL)SuspensionOphthalmicAlcon, Inc.1989-07-211989-07-21Us
International/Other Brands
Efflumidex (Allergan) / Fluaton (Allergan) / Flumetholon (Ferron) / Fluor-op (Novartis Ophthalmics) / Flurolon (Allergan) / FML Liquifilm (Allergan) / Foxone (Winston) / Fucin (Mey See) / Fuluson (Dae Wo) / Fumelon (Han Lim) / Humetoron (Kuk Je)
Categories
UNII
SV0CSG527L
CAS number
426-13-1
Weight
Average: 376.4617
Monoisotopic: 376.204987621
Chemical Formula
C22H29FO4
InChI Key
FAOZLTXFLGPHNG-KNAQIMQKSA-N
InChI
InChI=1S/C22H29FO4/c1-12-9-17-15-6-8-21(27,13(2)24)20(15,4)11-18(26)22(17,23)19(3)7-5-14(25)10-16(12)19/h5,7,10,12,15,17-18,26-27H,6,8-9,11H2,1-4H3/t12-,15-,17-,18-,19-,20-,21-,22-/m0/s1
IUPAC Name
(1R,2S,8S,10S,11S,14R,15S,17S)-14-acetyl-1-fluoro-14,17-dihydroxy-2,8,15-trimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-3,6-dien-5-one
SMILES
[H][C@@]12CC[C@](O)(C(C)=O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](C)C2=CC(=O)C=C[C@]12C

Pharmacology

Indication

For the ophthalmic treatment of corticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe.

Associated Conditions
Pharmacodynamics

Corticosteroids such as fluorometholone inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.

Mechanism of action

There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Their primary target is 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.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Side effects may include acute anterior uveitis and perforation of the globe. Keratitis, conjunctivitis, corneal ulcers, mydriasis, conjunctival hyperemia, loss of accommodation and ptosis have occasionally been reported following local use of corticosteroids. LD50 = 234 mg/kg (rats)

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

Fried, J.; U.S. Patent 2,852,51 September 16,1958; assigned to Olin Mathieson Chemical Corporation. 
Lincoln, F.H. Jr., Schneider, W.P. and Spero, G.B.; US. Patent 2,867,637; January 6, 1959; assigned to The Upjohn Company
. Lincoln, F.H. Jr., Schneider, W.P. and Spero, G.B.; U.S. Patent 2,867,638; January 6, 1959; assigned to The Upjohn Company. 
Magerlein, B.J., Kagan, F. and Schlagel, C.A.; U.S. Patent 3,038,914; June 12, 1962; assigned to The Upjohn Company.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014469
KEGG Drug
D01367
PubChem Compound
9878
PubChem Substance
46505984
ChemSpider
9494
ChEBI
31625
ChEMBL
CHEMBL1200600
Therapeutic Targets Database
DAP001047
PharmGKB
PA164781355
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Fluorometholone
ATC Codes
D07XB04 — FluorometholoneD10AA01 — FluorometholoneS01BA07 — FluorometholoneC05AA06 — FluorometholoneD07AB06 — FluorometholoneS01CB05 — FluorometholoneS01BB03 — Fluorometholone and mydriaticsD07CB03 — Fluorometholone and antibioticsS01CA07 — Fluorometholone and antiinfectives
AHFS Codes
  • 52:08.08 — Corticosteroids
FDA label
Download (64.7 KB)
MSDS
Download (72 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedPreventionBullous Keratopathy / Fuchs' Dystrophy1
2WithdrawnTreatmentLacrimation increased1
2, 3RecruitingPreventionCorneal Opacity1
3CompletedPreventionFibrosis / Glaucoma / Intraocular Pressure / Trabeculectomy1
3CompletedTreatmentEye Dryness1
4CompletedTreatmentIntraocular Pressure1
4Not Yet RecruitingTreatmentMust be PRK Candidate1
Not AvailableCompletedTreatmentBilamellar Tarsal Rotation / Trachoma / Trichiasis1
Not AvailableCompletedTreatmentModerate to Severe Dry Eye Syndrome1
Not AvailableCompletedTreatmentPterygium of the Conjunctiva and Cornea1
Not AvailableTerminatedNot AvailableDegeneration / Ectasia / Keratoconus2
Not AvailableUnknown StatusTreatmentEye Dryness1
Not AvailableWithdrawnTreatmentDescemet's Stripping Endothelial Keratoplasty / Endothelial Dystrophy / Posterior Lamellar Keratoplasty / Secondary Bullous Keratopathy1

Pharmacoeconomics

Manufacturers
  • Pharmacia and upjohn co
  • Allergan pharmaceutical
  • Novartis pharmaceuticals corp
  • Alcon laboratories inc
Packagers
  • Alcon Laboratories
  • Allergan Inc.
  • A-S Medication Solutions LLC
  • Bausch & Lomb Inc.
  • Dispensing Solutions
  • Novartis AG
  • OMJ Pharmaceuticals
  • Pacific Pharma Lp
  • Pharma Pac LLC
  • Pharmedix
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
SuspensionOphthalmic0.1 mL/100mL
Solution / dropsOphthalmic1 mg/1mL
OintmentOphthalmic1 mg/1g
Suspension / dropsOphthalmic1 mg/1mL
Solution / dropsOphthalmic0.1 %
Suspension / dropsOphthalmic2.5 mg/1mL
SuspensionOphthalmic0.25 %
SuspensionOphthalmic
SuspensionOphthalmic0.1 %
Prices
Unit descriptionCostUnit
FML Liquifilm 0.1% Suspension 15ml Bottle82.16USD bottle
FML Forte 0.25% Suspension 15ml Bottle60.98USD bottle
FML Liquifilm 0.1% Suspension 10ml Bottle60.17USD bottle
Flarex 0.1% Suspension 10ml Bottle50.7USD bottle
FML Forte 0.25% Suspension 10ml Bottle48.58USD bottle
Flarex 0.1% Suspension 5ml Bottle42.82USD bottle
FML Liquifilm 0.1% Suspension 5ml Bottle41.65USD bottle
FML-S Liquifilm 0.1-10% Suspension 10ml Bottle35.99USD bottle
Fluor-Op 0.1% Suspension 15ml Bottle30.99USD bottle
FML Forte 0.25% Suspension 5ml Bottle30.07USD bottle
Fluor-Op 0.1% Suspension 10ml Bottle25.99USD bottle
Fluor-Op 0.1% Suspension 5ml Bottle17.99USD bottle
Flarex 0.1% eye drops8.11USD ml
Fml liquifilm 0.1% eye drop6.27USD ml
Fml forte 0.25% eye drops5.09USD ml
Fluorometholone 0.1% drops3.25USD ml
Fml Forte 0.25 % Suspension2.96USD ml
Flarex 0.1 % Suspension1.96USD ml
Pms-Fluorometholone 0.1 % Suspension1.73USD ml
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)292-303Fried, J.; U.S. Patent 2,852,51 September 16,1958; assigned to Olin Mathieson Chemical Corporation. 
Lincoln, F.H. Jr., Schneider, W.P. and Spero, G.B.; US. Patent 2,867,637; January 6, 1959; assigned to The Upjohn Company
. Lincoln, F.H. Jr., Schneider, W.P. and Spero, G.B.; U.S. Patent 2,867,638; January 6, 1959; assigned to The Upjohn Company. 
Magerlein, B.J., Kagan, F. and Schlagel, C.A.; U.S. Patent 3,038,914; June 12, 1962; assigned to The Upjohn Company.
water solubility30 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.00HANSCH,C ET AL. (1995)
logS-4.1ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0166 mg/mLALOGPS
logP2.34ALOGPS
logP2.42ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)12.65ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity100.87 m3·mol-1ChemAxon
Polarizability40.05 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9956
Blood Brain Barrier+0.9716
Caco-2 permeable+0.8169
P-glycoprotein substrateSubstrate0.7834
P-glycoprotein inhibitor INon-inhibitor0.6791
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8397
CYP450 2C9 substrateNon-substrate0.8762
CYP450 2D6 substrateNon-substrate0.907
CYP450 3A4 substrateSubstrate0.7663
CYP450 1A2 substrateNon-inhibitor0.9149
CYP450 2C9 inhibitorNon-inhibitor0.8345
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9285
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9452
Ames testNon AMES toxic0.9025
CarcinogenicityNon-carcinogens0.9404
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3393 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9694
hERG inhibition (predictor II)Non-inhibitor0.5956
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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/MSsplash10-0079-2960000000-57c1831d283834b32701

Taxonomy

Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 11-beta-hydroxysteroids / 17-hydroxysteroids / Halogenated steroids / 3-oxo delta-1,4-steroids / Delta-1,4-steroids / Tertiary alcohols / Alpha-hydroxy ketones / Secondary alcohols / Fluorohydrins
show 6 more
Substituents
Progestogin-skeleton / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 17-hydroxysteroid / 11-hydroxysteroid / 11-beta-hydroxysteroid / Oxosteroid / 9-halo-steroid / Halo-steroid
show 21 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
11beta-hydroxy steroid, 17alpha-hydroxy steroid, glucocorticoid, 20-oxo steroid, fluorinated steroid, 3-oxo-Delta(1),Delta(4)-steroid (CHEBI:31625)

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. Samudre SS, Lattanzio FA Jr, Williams PB, Sheppard JD Jr: Comparison of topical steroids for acute anterior uveitis. J Ocul Pharmacol Ther. 2004 Dec;20(6):533-47. [PubMed:15684812]
  2. Grossman R, Yehuda R, Golier J, McEwen B, Harvey P, Maria NS: Cognitive effects of intravenous hydrocortisone in subjects with PTSD and healthy control subjects. Ann N Y Acad Sci. 2006 Jul;1071:410-21. [PubMed:16891588]
  3. Rautanen A, Eriksson JG, Kere J, Andersson S, Osmond C, Tienari P, Sairanen H, Barker DJ, Phillips DI, Forsen T, Kajantie E: Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene. J Clin Endocrinol Metab. 2006 Nov;91(11):4544-51. Epub 2006 Aug 8. [PubMed:16895953]
  4. Hammer F, Stewart PM: Cortisol metabolism in hypertension. Best Pract Res Clin Endocrinol Metab. 2006 Sep;20(3):337-53. [PubMed:16980198]
  5. Shaw JR, Gabor K, Hand E, Lankowski A, Durant L, Thibodeau R, Stanton CR, Barnaby R, Coutermarsh B, Karlson KH, Sato JD, Hamilton JW, Stanton BA: Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic. Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R1052-60. Epub 2006 Oct 12. [PubMed:17038445]
  6. Sher L: Combined dexamethasone suppression-corticotropin-releasing hormone stimulation test in studies of depression, alcoholism, and suicidal behavior. ScientificWorldJournal. 2006 Oct 31;6:1398-404. [PubMed:17086345]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. El-Sankary W, Bombail V, Gibson GG, Plant N: Glucocorticoid-mediated induction of CYP3A4 is decreased by disruption of a protein: DNA interaction distinct from the pregnane X receptor response element. Drug Metab Dispos. 2002 Sep;30(9):1029-34. [PubMed:12167569]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:40