DIFLUPREDNATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H34F2O7
Molecular Weight	508.5515
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=WYQPLTPSGFELIB-JTQPXKBDSA-N

InChI=1S/C27H34F2O7/c1-5-6-23(34)36-26(22(33)14-35-15(2)30)10-8-17-18-12-20(28)19-11-16(31)7-9-24(19,3)27(18,29)21(32)13-25(17,26)4/h7,9,11,17-18,20-21,32H,5-6,8,10,12-14H2,1-4H3/t17-,18-,20-,21-,24-,25-,26-,27-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB06781
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022212s000_Lbl.pdf

Difluprednate is a corticosteroid used as an anti-inflammatory steroidal drug used primarily in ocular surgery. It is thought to act by the induction of phospholipase A2 inhibitory proteins (lipocortins). It is postulated that these proteins control the biosynthesis of potent mediators of infammation 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. It is marketed by Alcon under the tradename Durezol.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glucocorticoid receptor 172 Target ID: CHEMBL2034 Sources: http://www.drugbank.ca/drugs/DB06781	Agonist 2678		0.57 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Endogenous anterior uveitis 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022212s000_Lbl.pdf	Primary		Approved 8429	Durezol Approved Use Durezol® (difluprednate ophthalmic emulsion) 0.05%, a topical corticosteroid, is indicated for the treatment of inflammation and pain associated with ocular surgery. Durezol is also indicated for the treatment of endogenous anterior uveitis. Launch Date 1.2140928E12

C_max

Value	Dose	Co-administered	Analyte	Population
3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21182429/	2.5 μL single, ocular dose: 2.5 μL route of administration: Ocular experiment type: SINGLE co-administered:		DIFLUPREDNATE plasma	Oryctolagus cuniculus population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
8.61 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21182429/	2.5 μL single, ocular dose: 2.5 μL route of administration: Ocular experiment type: SINGLE co-administered:		DIFLUPREDNATE plasma	Oryctolagus cuniculus population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21182429/	2.5 μL single, ocular dose: 2.5 μL route of administration: Ocular experiment type: SINGLE co-administered:		DIFLUPREDNATE plasma	Oryctolagus cuniculus population: HEALTHY age: ADULT sex: MALE food status: FED

Doses

Dose	Population	Adverse events
1 drop 9 times / day multiple, topical Highest studied dose Dose: 1 drop, 9 times / day Route: topical Route: multiple Dose: 1 drop, 9 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31712024 Page: p.2	unhealthy, 56.7 ± 17.9 n = 33 Health Status: unhealthy Condition: Corneal graft rejection Age Group: 56.7 ± 17.9 Sex: M+F Population Size: 33 Sources: https://pubmed.ncbi.nlm.nih.gov/31712024 Page: p.2	Disc. AE: Intraocular pressure increased, Toxic epitheliolysis... AEs leading to discontinuation/dose reduction: Intraocular pressure increased (18.2%) Toxic epitheliolysis (grade 1-2, 21.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/31712024 Page: p.2
1 drop 4 times / day multiple, topical Recommended Dose: 1 drop, 4 times / day Route: topical Route: multiple Dose: 1 drop, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Inflammation and pain associated with ocular surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2	Other AEs: IOP increased, Cataract... Other AEs: IOP increased Cataract Healing delayed Bacterial infection Infection viral Fungal infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2

AEs

AE	Significance	Dose	Population
Intraocular pressure increased	18.2% Disc. AE	1 drop 9 times / day multiple, topical Highest studied dose Dose: 1 drop, 9 times / day Route: topical Route: multiple Dose: 1 drop, 9 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31712024 Page: p.2	unhealthy, 56.7 ± 17.9 n = 33 Health Status: unhealthy Condition: Corneal graft rejection Age Group: 56.7 ± 17.9 Sex: M+F Population Size: 33 Sources: https://pubmed.ncbi.nlm.nih.gov/31712024 Page: p.2
Toxic epitheliolysis	grade 1-2, 21.2% Disc. AE	1 drop 9 times / day multiple, topical Highest studied dose Dose: 1 drop, 9 times / day Route: topical Route: multiple Dose: 1 drop, 9 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31712024 Page: p.2	unhealthy, 56.7 ± 17.9 n = 33 Health Status: unhealthy Condition: Corneal graft rejection Age Group: 56.7 ± 17.9 Sex: M+F Population Size: 33 Sources: https://pubmed.ncbi.nlm.nih.gov/31712024 Page: p.2
Bacterial infection		1 drop 4 times / day multiple, topical Recommended Dose: 1 drop, 4 times / day Route: topical Route: multiple Dose: 1 drop, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Inflammation and pain associated with ocular surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2
Cataract		1 drop 4 times / day multiple, topical Recommended Dose: 1 drop, 4 times / day Route: topical Route: multiple Dose: 1 drop, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Inflammation and pain associated with ocular surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2
Fungal infection		1 drop 4 times / day multiple, topical Recommended Dose: 1 drop, 4 times / day Route: topical Route: multiple Dose: 1 drop, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Inflammation and pain associated with ocular surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2
Healing delayed		1 drop 4 times / day multiple, topical Recommended Dose: 1 drop, 4 times / day Route: topical Route: multiple Dose: 1 drop, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Inflammation and pain associated with ocular surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2
IOP increased		1 drop 4 times / day multiple, topical Recommended Dose: 1 drop, 4 times / day Route: topical Route: multiple Dose: 1 drop, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Inflammation and pain associated with ocular surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2
Infection viral		1 drop 4 times / day multiple, topical Recommended Dose: 1 drop, 4 times / day Route: topical Route: multiple Dose: 1 drop, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Inflammation and pain associated with ocular surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022212lbl.pdf Page: p.2

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA0039JI	https://www.aablocks.com/goods/Goods/detail?id=AA0039JI
AHH Chemical co.,ltd	API-1837	http://www.ahhchemical.com/product/API-1837.html
AK Scientific, Inc. (AKSCI)	Q827	http://www.aksci.com/item_detail.php?cat=Q827
Aaron Chemicals	AR003ABA	http://www.aaronchem.com/23674-86-4
AbMole Bioscience	M2638	http://www.abmole.com/products/difluprednate.html
Alfa Chemistry	23674-86-4	https://www.alfa-chemistry.com/difluprednate-cas-23674-86-4-item-291085.htm
ApexBio Technology	B1728	http://www.apexbt.com/difluprednate.html
Aurora Fine Chemicals LLC	A17.880.480	http://online.aurorafinechemicals.com/info?ID=A17.880.480
BioSynth	Q-101389	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-101389.html
Chem Scene	CS-3001	http://www.chemscene.com/23674-86-4.html
Chemspace	CSSB00025701745	https://chem-space.com/CSSB00025701745
Combi-Blocks	QW-8173	http://www.combi-blocks.com/cgi-bin/find.cgi?QW-8173
DC Chemicals	DC9551	http://www.dcchemicals.com/product_show-Difluprednate.html
Glentham Life Sciences	GP3988	http://www.glentham.com/products/product/GP3988/
Hairui	HR122430	http://www.hairuichem.com/en/product/23674-86-4.html
LGC Standards	MM3567.00	https://www.lgcstandards.com/US/en/p/MM3567.00
Lab Network	LN01287539	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01287539
MedChem Express	HY-17569	https://www.medchemexpress.com/Difluprednate.html
MuseChem	A000854	https://www.musechem.com/product/A000854.html
OChem	17207	http://www.ocheminc.com/index.php?act=psearch&pid=674D864
Sigma-Aldrich	D6288_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/d6288?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S795563	https://www.smolecule.com/products/s795563
abcr GmbH	AB493672	http://www.abcr.com/shop/en/AB493672
eNovation Chemicals	D674475	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674475
iChemical	EBD19511	http://www.ichemical.com/products/23674-86-4.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Neuronal cell bodies in the hypothalamic paraventricular nucleus mediate stress-induced renin and corticosterone secretion.	1989 Jul	2666872
The role of difluprednate ophthalmic emulsion in clinical practice.	2009	19668594
Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain.	2009 Jan	19101421
Pharmacokinetic features of difluprednate ophthalmic emulsion in rabbits as determined by glucocorticoid receptor-binding bioassay.	2011 Feb	21182429

Patents

Sample Use Guides

In Vivo Use Guide

Ocular Surgery Instill one drop into the conjunctival sac of the affected eye 4 times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period, followed by 2 times daily for a week and then a taper based on the response. Endogenous Anterior Uveitis Instill one drop into the conjunctival sac of the affected eye 4 times daily for 14 days followed by tapering as clinically indicated.

Route of Administration: Topical

In Vitro Use Guide

Difluprednate exhibited GR agonistic activity in GR-CALUX assay with EC50 value 0.57nM

Name

Type

Language

DIFLUPREDNATE

Official Name

English

difluprednate [INN]

Common Name

English

DIFLUPREDNATE [USAN]

Common Name

English

6α,9-Difluoro-11β,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate 17-butyrate

Common Name

English

DIFLUPREDNATE [VANDF]

Common Name

English

DIFLUPREDNATE [MI]

Common Name

English

DUREZOL

Brand Name

English

Difluprednate [WHO-DD]

Common Name

English

W 6309

Code

English

DIFLUPREDNATE [JAN]

Common Name

English

W-6309

Code

English

DIFLUPREDNATE [MART.]

Common Name

English

PREGNA-1,4-DIENE-3,20-DIONE, 21-(ACETYLOXY)-6,9-DIFLUORO-11-HYDROXY-17-(1-OXOBUTOXY)-, (6.ALPHA.,11.BETA.)-

Systematic Name

English

DIFLUPREDNATE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C521