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Identification
NameFluorometholone
Accession NumberDB00324  (APRD00980)
TypeSmall Molecule
GroupsApproved
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
Fluor-OP
Fluorometholon
Fluorométholone
Fluorometholone
Fluorometholonum
Fluorometolona
NSC 33001
Oxylone
External Identifiers
  • U 17323
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Flarexsuspension/ drops1 mg/mLophthalmicAlcon Laboratories, Inc.1992-02-06Not applicableUs
Flarex Oph Susp 0.1%suspension0.1 %ophthalmicAlcon Canada Inc1987-12-31Not applicableCanada
Fluorometholonesolution/ drops1 mg/mLophthalmicPacific Pharma, Inc.1997-10-31Not applicableUs
FMLointment1 mg/gophthalmicAllergan, Inc.1985-12-09Not applicableUs
FMLsuspension/ drops1 mg/mLophthalmicAllergan, Inc.1972-02-01Not applicableUs
FML 0.1%drops0.1 %ophthalmicAllergan Inc1972-12-31Not applicableCanada
FML Fortesuspension/ drops2.5 mg/mLophthalmicAllergan, Inc.1986-05-01Not applicableUs
FML Forte Sus 0.25%suspension0.25 %ophthalmicAllergan Inc1987-12-312016-04-06Canada
PMS-fluorometholonesuspension0.1 %ophthalmicPharmascience Inc2001-07-16Not applicableCanada
Sandoz Fluorometholonesuspension0.1 %ophthalmicSandoz Canada Incorporated2012-07-24Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
EfflumidexAllergan
FluatonAllergan
FlumetholonFerron
Fluor-opNovartis Ophthalmics
FlurolonAllergan
FML LiquifilmAllergan
FoxoneWinston
FucinMey See
FulusonDae Wo
FumelonHan Lim
HumetoronKuk Je
Brand mixtures
NameLabellerIngredients
FML-neo Oph SusAllergan Inc
Salts
Name/CASStructureProperties
Fluorometholone Acetate
ThumbNot applicableDBSALT001065
Categories
UNIISV0CSG527L
CAS number426-13-1
WeightAverage: 376.4617
Monoisotopic: 376.204987621
Chemical FormulaC22H29FO4
InChI KeyInChIKey=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[[email protected]](O)[C@@]1(F)[C@@]2([H])C[[email protected]](C)C2=CC(=O)C=C[C@]12C
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassPregnane steroids
Direct ParentGluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
Substituents
  • Progestogin-skeleton
  • 20-oxosteroid
  • 17-hydroxysteroid
  • 11-hydroxysteroid
  • 11-beta-hydroxysteroid
  • Oxosteroid
  • Hydroxysteroid
  • Halo-steroid
  • 9-halo-steroid
  • 3-oxosteroid
  • 3-oxo-delta-1,4-steroid
  • Delta-1,4-steroid
  • Tertiary alcohol
  • Cyclic alcohol
  • Alpha-hydroxy ketone
  • Cyclic ketone
  • Secondary alcohol
  • Ketone
  • Halohydrin
  • Fluorohydrin
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl fluoride
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the ophthalmic treatment of corticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe.
PharmacodynamicsCorticosteroids 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 actionThere 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySide 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
  • Allergan pharmaceutical
  • Novartis pharmaceuticals corp
  • Alcon laboratories inc
Packagers
Dosage forms
FormRouteStrength
Solution/ dropsophthalmic1 mg/mL
Ointmentophthalmic1 mg/g
Suspension/ dropsophthalmic1 mg/mL
Dropsophthalmic0.1 %
Suspension/ dropsophthalmic2.5 mg/mL
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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point292-303Fried, 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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot 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 ReferencesNot Available
External Links
ATC CodesC05AA06D07AB06D07CB03D07XB04D10AA01S01BA07S01BB03S01CA07S01CB05
AHFS Codes
  • 52:08.08
PDB EntriesNot Available
FDA labelDownload (64.7 KB)
MSDSDownload (72 KB)
Interactions
Drug Interactions
Drug
AldesleukinFluorometholone may decrease the antineoplastic activities of Aldesleukin.
CeritinibFluorometholone may increase the hyperglycemic activities of Ceritinib.
Corticorelin ovine triflutateThe therapeutic efficacy of Corticorelin can be decreased when used in combination with Fluorometholone.
DeferasiroxThe risk or severity of adverse effects can be increased when Fluorometholone is combined with Deferasirox.
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Fluorometholone.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Fluorometholone.
Food InteractionsNot 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 modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon grow...
Gene Name:
NR3C1
Uniprot ID:
P04150
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
substrateinducer
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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
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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on April 23, 2014 16:04