FLUOROMETHOLONE ACETATE

First approved in 1959

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H31FO5
Molecular Weight	418.4983
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@](OC(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=YRFXGQHBPBMFHW-SBTZIJSASA-N

InChI=1S/C24H31FO5/c1-13-10-19-17-7-9-23(14(2)26,30-15(3)27)22(17,5)12-20(29)24(19,25)21(4)8-6-16(28)11-18(13)21/h6,8,11,13,17,19-20,29H,7,9-10,12H2,1-5H3/t13-,17-,19-,20-,21-,22-,23-,24-/m0/s1

HIDE SMILES / InChI

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
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
Subconjunctival crystals in paediatric blepharokeratoconjunctivitis.	2006 Aug	16879584
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 variant N363S of glucocorticoid receptor in steroid-induced ocular hypertension in Hungarian patients treated with photorefractive keratectomy.	2007 Apr 27	17563720
The effect of topical diclofenac on choroidal blood flow in early postoperative pseudophakias with regard to cystoid macular edema formation.	2007 Dec	18055815
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
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
Mitomycin C in photorefractive keratectomy: effect on epithelialization and predictability.	2008 Apr	18362654
Bacterial keratitis after nonpenetrating glaucoma surgery.	2008 Apr	18361998
Delayed-onset Actinomyces keratitis after laser in situ keratomileusis.	2008 Aug	18650675
Delayed epithelial ingrowth caused by viral conjunctivitis after LASIK.	2008 Aug 30	18729311
A case of epithelial inclusion cyst of iris.	2008 Dec	19096245
Posttraumatic Stenotrophomonas maltophilia infectious scleritis.	2008 Feb	18216585
Aggravated dry eye after laser in situ keratomileusis in patients with Sjögren syndrome.	2008 Jan	18245981
Treatment of recurrent corneal erosion syndrome using the combination of oral doxycycline and topical corticosteroid.	2008 Jan-Feb	18290949
Juvenile xanthogranuloma of the corneal limbus: report of two cases and review of the literature.	2008 Jul	18580271
Phosphate concentration in ophthalmic corticoid preparations.	2008 Jul	18357463
Post-penetrating keratoplasty glaucoma.	2008 Jul-Aug	18579984
Recurrent occlusion of laser iridotomy sites after posterior chamber phakic IOL implantation.	2008 Jun	18612232
A simple new method for identifying the proximal cut end in lower canalicular laceration.	2008 Jun	18612222
Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy.	2008 Mar 28	18373855
Short-term effect of topical brinzolamide on human central corneal thickness.	2008 May-Jun	18465712
Effect of nepafenac sodium 0.1% on delayed corneal epithelial healing and haze after photorefractive keratectomy: retrospective comparative study.	2008 Sep	18721717
[Post-traumatic striate melanokeratosis in a Caucasian woman].	2009 Apr	19384762
Effect of chitosan-N-acetylcysteine conjugate in a mouse model of botulinum toxin B-induced dry eye.	2009 Apr	19365035
Mitomycin-C in hyperopic photorefractive keratectomy.	2009 Apr	19304089
Steroid-induced intraocular pressure elevation or glaucoma after penetrating keratoplasty in patients with keratoconus or Fuchs dystrophy.	2009 Aug	19574912
Efficacy of olopatadine HCI 0.1%, ketotifen fumarate 0.025%, epinastine HCI 0.05%, emedastine 0.05% and fluorometholone acetate 0.1% ophthalmic solutions for seasonal allergic conjunctivitis: a placebo-controlled environmental trial.	2009 Aug	18631332
Diagnosis of steroid-induced elevated intraocular pressure and associated lamellar keratitis after laser in situ keratomileusis using optical coherence tomography.	2009 Feb	19185259
Scleral ulceration after vitreoretinal surgery.	2009 Jul-Aug	19574702
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
The evaluation of the treatment response in obstructive meibomian gland disease by in vivo laser confocal microscopy.	2009 Jun	19101718
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
Safety and efficacy of Intacs in Indian eyes with keratoconus: an initial report.	2009 Mar-Apr	19237784

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.

Name

Type

Language

FLUOROMETHOLONE ACETATE

Official Name

English

FLUOROMETHOLONE ACETATE [ORANGE BOOK]

Common Name

English

FLAREX

Brand Name

English

FLUOROMETHOLONE ACETATE [MART.]

Common Name

English

FLUOROMETHOLONE ACETATE [USP-RS]

Common Name

English

FLUOROMETHOLONE ACETATE [VANDF]

Common Name

English

FLUOROMETHOLONE ACETATE [USAN]

Common Name

English

U-17323

Code

English

U-17,323

Code

English

Fluorometholone acetate [WHO-DD]

Common Name

English

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

Systematic Name

English

FLUOROMETHOLONE 17-ACETATE [MI]

Common Name

English

FLUOROMETHOLONE 17-ACETATE

Common Name

English

NSC-47438

Code

English

TOBRASONE COMPONENT FLUOROMETHOLONE ACETATE

Common Name

English

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

Systematic Name

English

FLUOROMETHOLONE ACETATE COMPONENT OF TOBRASONE

Common Name

English

FLUOROMETHOLONE ACETATE [USP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C521