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
Simultaneous determination of betamethasone and dexamethasone residues in bovine liver by liquid chromatography/tandem mass spectrometry.	2001	11382932
Ligneous conjunctivitis: a case report.	2001 Jul-Aug	11485769
Tear tryptase in vernal keratoconjunctivitis.	2001 Mar	11231766
Detection of measles virus genomic RNA in tear samples from a patient with measles keratitis.	2002 Aug	12131042
Mechanism and treatments of regression and haze after photorefractive keratectomy.	2002 Jul	12411007
Effects of topical anti-inflammatory and antiallergic eyedrops on prostaglandin E2-induced aqueous flare elevation in pigmented rabbits.	2002 Jul	12096966
[Characteristics of pharmacodynamics of drugs after excimer laser surgery (an experimental study)].	2002 May-Jun	12226977
Confocal microscopic examination of trabecular meshwork removed during ab externo trabeculectomy.	2002 Sep	12185136
Bilateral methicillin-resistant staphylococcus aureus keratitis in a medical resident following an uneventful bilateral photorefractive keratectomy.	2003 Jul	12861116
Insect wing conjunctival granuloma.	2003 Jul	12827059
In vitro drug-induced spoliation of a keratoprosthetic hydrogel.	2004 Aug	15257003
Thygeson's superficial punctate keratitis recurrence after laser in situ keratomileusis.	2004 Sep	15364251
Visual quality after wavefront-guided LASIK for myopia.	2005 Oct	16224163
The effect of topical diclofenac on choroidal blood flow in early postoperative pseudophakias with regard to cystoid macular edema formation.	2007 Dec	18055815
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
Bacterial keratitis after nonpenetrating glaucoma surgery.	2008 Apr	18361998

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