FLUOROMETHOLONE

First approved in 1959

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H29FO4
Molecular Weight	376.4617
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@](O)(C(C)=O)[C@@]1(C)C[C@H](O)[C@@]3(F)[C@@]2([H])C[C@H](C)C4=CC(=O)C=C[C@]34C

InChI

InChIKey=FAOZLTXFLGPHNG-KNAQIMQKSA-N

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

HIDE SMILES / InChI

Molecular Formula	C22H29FO4
Molecular Weight	376.4617
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	8 / 8
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016851s063lbl.pdf
Curator's Comment: description was created based on several sources, including

Fluorometholone is a glucocorticoid employed, usually as eye drops, in the treatment of allergic and inflammatory conditions of the eye. Corticosteroids such as fluorometholone inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. 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. Corticosteroids are capable of producing a rise in intraocular pressure. In clinical studies of documented steroid-responders, fluorometholone demonstrated a significantly longer average time to produce a rise in intraocular pressure than dexamethasone phosphate.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glucocorticoid receptor 172 Target ID: CHEMBL2034 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15684812	Agonist 2678
Glucocorticoid receptor 172 Target ID: CHEMBL2034 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7073584	Binding Agent 1064

Conditions

Condition	Modality	Targets	Highest Phase	Product
Inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016851s063lbl.pdf	Primary		Approved 8429	FML Approved Use FML ® ointment is indicated for the treatment of corticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe. Launch Date 1972

Doses

Dose	Population	Adverse events
0.1 % 4 times / day steady, ophthalmic Dose: 0.1 %, 4 times / day Route: ophthalmic Route: steady Dose: 0.1 %, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30267699	healthy, 41.7 years n = 76 Health Status: healthy Age Group: 41.7 years Sex: M+F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/30267699	DLT: Allergic reaction... Disc. AE: Intraocular pressure increased... Dose limiting toxicities: Allergic reaction (1 patient) AEs leading to discontinuation/dose reduction: Intraocular pressure increased (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30267699
0.25 % 3 times / day steady, ophthalmic Recommended Dose: 0.25 %, 3 times / day Route: ophthalmic Route: steady Dose: 0.25 %, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019216s025lbl.pdf	unhealthy Health Status: unhealthy Condition: orticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019216s025lbl.pdf	Disc. AE: Glaucoma, Posterior subcapsular cataract... AEs leading to discontinuation/dose reduction: Glaucoma Posterior subcapsular cataract Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019216s025lbl.pdf

AEs

AE	Significance	Dose	Population
Allergic reaction	1 patient DLT, Disc. AE	0.1 % 4 times / day steady, ophthalmic Dose: 0.1 %, 4 times / day Route: ophthalmic Route: steady Dose: 0.1 %, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30267699	healthy, 41.7 years n = 76 Health Status: healthy Age Group: 41.7 years Sex: M+F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/30267699
Intraocular pressure increased	1 patient Disc. AE	0.1 % 4 times / day steady, ophthalmic Dose: 0.1 %, 4 times / day Route: ophthalmic Route: steady Dose: 0.1 %, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30267699	healthy, 41.7 years n = 76 Health Status: healthy Age Group: 41.7 years Sex: M+F Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/30267699
Glaucoma	Disc. AE	0.25 % 3 times / day steady, ophthalmic Recommended Dose: 0.25 %, 3 times / day Route: ophthalmic Route: steady Dose: 0.25 %, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019216s025lbl.pdf	unhealthy Health Status: unhealthy Condition: orticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019216s025lbl.pdf
Posterior subcapsular cataract	Disc. AE	0.25 % 3 times / day steady, ophthalmic Recommended Dose: 0.25 %, 3 times / day Route: ophthalmic Route: steady Dose: 0.25 %, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019216s025lbl.pdf	unhealthy Health Status: unhealthy Condition: orticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019216s025lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Nav1.5 97	P-gp 1537

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://cdnsciencepub.com/doi/abs/10.1139/o94-075 Page: 567.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Nav1.5 100	inhibitor 1626 Sources: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/j.1476-5381.2011.01415.x Page: 262.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31625	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31625
MolPort	MolPort-003-941-413	https://www.molport.com/shop/molecule-link/MolPort-003-941-413
ZINC	ZINC000118912517	http://zinc15.docking.org/substances/ZINC000118912517
eMolecules	30316174	https://www.emolecules.com/cgi-bin/more?vid=30316174
eMolecules	538523	https://www.emolecules.com/cgi-bin/more?vid=538523

PubMed

Title	Date	PubMed
Ocular-hypertensive and anti-inflammatory response to rimexolone therapy in children.	2003 Dec	14662591
Effect of FK506 eye drops on late and delayed-type responses in ocular allergy models.	2003 Nov	14616868
Effects of topical corticosteroids and nonsteroidal anti-inflammatory drugs on prostaglandin e2-induced aqueous flare elevation in pigmented rabbits.	2003 Nov-Dec	14688425
Corneal wound healing after laser in situ keratomileusis flap lift and epithelial abrasion.	2003 Oct	14604726
The comparison of efficacies of topical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: a clinical and immunocytochemical study.	2003 Oct	14516798
In vitro drug-induced spoliation of a keratoprosthetic hydrogel.	2004 Aug	15257003
Effect of topical 0.1% indomethacin solution versus 0.1% fluorometholon acetate on ocular surface and pain control following laser subepithelial keratomileusis (LASEK).	2004 Aug	15256991
Comparison of topical steroids for acute anterior uveitis.	2004 Dec	15684812
Quantitative, highly sensitive liquid chromatography-tandem mass spectrometry method for detection of synthetic corticosteroids.	2004 Dec	15486026
Ocular rosacea in childhood.	2004 Jan	14700657
[A retrospective analysis of infection after corneal transplantation].	2004 Jun	15242070
Evaluation of ophthalmic suspensions using surface tension.	2004 Mar	15018999
Acute asthma attack caused by ophthalmic application of antiallergic agents.	2004 Sep-Oct	15486771
The efficacy of hourly prophylactic steroids in diffuse lamellar keratitis epidemic.	2004 Sep-Oct	15334012
US trends in refractive surgery: 2003 ISRS/AAO survey.	2005 Jan-Feb	15724690
Experimental study of an automated system for the delivery of eyedrops using a microinfusion pump.	2005 Mar	15767073
Disappearance of honeycomb opacity of Thiel-Behnke corneal dystrophy after Thygeson superficial punctate keratitis.	2005 Nov	16227859
Visual quality after wavefront-guided LASIK for myopia.	2005 Oct	16224163
[Intraocular pressure after ND: YAG laser capsulotomy in pseudophakic patients with glaucoma].	2006	16848199
Effects of antibiotics and corticosteroid eyedrops on cellular proliferation in cultured human corneal keratocytes.	2006 Aug	16911920
Haze after photorefractive keratectomy caused by iatrogenic lagophthalmos.	2006 Aug	16863982
A clinical study of the efficacy of topical corticosteroids on dry eye.	2006 Aug	16845723
Corneal perforation during laser blepharoplasty.	2006 Jul-Aug	16898397
Comparison of laser epithelial keratomileusis with and without the use of mitomycin C.	2006 Oct	17061715
Conjunctival mucoepidermoid carcinoma in a patient with ocular cicatricial pemphigoid and a review of the literature.	2006 Sep-Oct	16950250
The effect of topical diclofenac on choroidal blood flow in early postoperative pseudophakias with regard to cystoid macular edema formation.	2007 Dec	18055815
Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca.	2007 Feb	17341147
The safety of 250 microm residual stromal bed in preventing keratectasia after laser in situ keratomileusis (LASIK).	2007 Feb	17297268
Comparison of topical dry eye medications for the treatment of keratoconjunctivitis sicca in a botulinum toxin B-induced mouse model.	2007 Jan	17198019
Multifocal lamellar keratitis following laser in situ keratomileusis.	2007 Jan	17189812
Isolated large limbal nodule as the presenting feature of vernal keratoconjunctivitis.	2007 Jan-Feb	17274337
Diagnosis and management of Thygeson's superficial punctate keratitis.	2007 Jul	17601570
Preclinical investigation of fluorometholone acetate as a potential new adjuvant during vitreous surgery.	2007 Jul	17186258
Effect of base curve radius of therapeutic lenses on epithelial healing after laser-assisted subepithelial keratectomy.	2007 Jun	17592238
Lacrimal gland inflammatory cytokine gene expression in the botulinum toxin B-induced murine dry eye model.	2007 Nov 29	18087241
Bilateral peripheral infiltrative keratitis after LASIK.	2007 Sep	17804925
Infectious crystalline keratopathy caused by Serratia marcescens.	2007 Sep	17721309
Diagnosis of steroid-induced glaucoma after photorefractive keratectomy.	2008 Apr	18500094
Posttraumatic Stenotrophomonas maltophilia infectious scleritis.	2008 Feb	18216585
Aggravated dry eye after laser in situ keratomileusis in patients with Sjögren syndrome.	2008 Jan	18245981
Post-penetrating keratoplasty glaucoma.	2008 Jul-Aug	18579984
Effect of nepafenac sodium 0.1% on delayed corneal epithelial healing and haze after photorefractive keratectomy: retrospective comparative study.	2008 Sep	18721717
Effect of chitosan-N-acetylcysteine conjugate in a mouse model of botulinum toxin B-induced dry eye.	2009 Apr	19365035
Steroid-induced intraocular pressure elevation or glaucoma after penetrating keratoplasty in patients with keratoconus or Fuchs dystrophy.	2009 Aug	19574912
Diagnosis of steroid-induced elevated intraocular pressure and associated lamellar keratitis after laser in situ keratomileusis using optical coherence tomography.	2009 Feb	19185259
Dry eye after cataract surgery and associated intraoperative risk factors.	2009 Jun	19568353
Comparison of efficacy of bromfenac sodium 0.1% ophthalmic solution and fluorometholone 0.02% ophthalmic suspension for the treatment of allergic conjunctivitis.	2009 Jun	19348602
Topical and oral voriconazole in the treatment of fungal keratitis.	2009 Mar	19337480
Intravitreal triamcinolone acetonide injection at the time of pars plana vitrectomy for retained lens material.	2009 Mar	19337473
Validation of a solid-phase extraction and ultra-performance liquid chromatographic tandem mass spectrometric method for the detection of 16 glucocorticoids in pig tissues.	2009 Mar-Apr	19485221

Patents

Sample Use Guides

In Vivo Use Guide

Instill one drop into the conjunctival sac two to four times daily. During the initial 24 to 48 hours, the dosing frequency may be increased to one application every four hours

Route of Administration: Other

In Vitro Use Guide

IC50 values for hCA-I (Carbonic anhydrase I) and hCA-II were 11.7, 0.11 μm using fluorometholone acetate. For fluorometholone acetate and dexamethasone, Ki values from Lineweaver-Burk plots were obtained as 1.044 and 21.2 μm (noncompetitive) for hCA-I and 9.98 and 8.66 μm (non-competitive) for hCA-II. Fluorometholone acetate showed potent inhibitory effects on esterase activity of hCA-I and hCA-II isozymes.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:04:21 GMT 2023` Edited by `admin` on `Sat Dec 16 16:04:21 GMT 2023`
Record UNII	SV0CSG527L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FLUOROMETHOLONE

Official Name

English

FML

Brand Name

English

fluorometholone [INN]

Common Name

English

FLUOROMETHOLONE COMPONENT OF FML-S

Common Name

English

FLUOROMETHOLONE [MI]

Common Name

English

OXYLONE

Brand Name

English

FLUOROMETHOLONE [VANDF]

Common Name

English

9-Fluoro-11β,17-dihydroxy-6α-methylpregna-1,4-diene-3,20-dione

Systematic Name

English

Fluorometholone [WHO-DD]

Common Name

English

PREGNA-1,4-DIENE-3,20-DIONE, 9-FLUORO-11,17-DIHYDROXY-6-METHYL-, (6.ALPHA.,11.BETA.)-

Systematic Name

English

FLUOR-OP

Brand Name

English

FML-S COMPONENT FLUOROMETHOLONE

Common Name

English

NSC-33001

Code

English

FLUOROMETHOLONE [USP-RS]

Common Name

English

FLUOROMETHOLONE [USP MONOGRAPH]

Common Name

English

FLUOROMETHOLONE [JAN]

Common Name

English

FLUOROMETHOLONE [ORANGE BOOK]

Common Name

English

FLUOROMETHOLONE [MART.]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175450