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Identification
- Summary
Difluprednate is a topical corticosteroid used for the symptomatic treatment of inflammation and pain associated with ocular surgery.
- Brand Names
- Durezol
- Generic Name
- Difluprednate
- DrugBank Accession Number
- DB06781
- Background
Difluprednate is a topical corticosteroid indicated for the treatment of infammation and pain associated with ocular surgery. It is a butyrate ester of 6(α), 9(α)-difluoro prednisolone acetate. Difluprednate is abbreviated DFBA, or difluoroprednisolone butyrate acetate. It is indicated for treatment of endogenous anterior uveiti.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Difluprednate (DB06781)
- Weight
- Average: 508.5515
Monoisotopic: 508.227259852 - Chemical Formula
- C27H34F2O7
- Synonyms
- DFBA
- Difluoroprednisolone butyrate acetate
- Difluprednate
- External IDs
- W 6309
- W-6309
Pharmacology
- Indication
For the treatment of inflammation and pain associated with ocular surgery.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Anterior uveitis •••••••••••• •••••••••• Treatment of Endogenous anterior uveitis •••••••••••• ••••••••• •••••••• Treatment of Eye pain •••••••••••• ••• ••••••• ••••••••• •••••••• Treatment of Eye inflammation •••••••••••• ••• ••••••• ••••••••• •••••••• Treatment of Pain of the eye •••••••••••• •••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Difluprednate is a corticosteroid used as an anti-inflammatory steroidal drug used primarily in ocular surgery.
- Mechanism of action
Corticosteroids are 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.
Target Actions Organism AGlucocorticoid receptor agonistHumans AAnnexin A1 agonistHumans - Absorption
Difluprednate penetrates the corneal epithelium rapidly and effectively. Low systemic absorption.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Difluprednate is rapidly deacetylated in the aqueous humor to difluoroprednisolone butyrate (DFB), the drug’s active metabolite. Endogenous tissue esterases then metabolize DFB to the inert metabolite hydroxyfluoroprednisolone butyrate (HFB), which limits systemic exposure to the active compound.
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- Route of elimination
78.5% of radioactivity was excreted aftert 24 hours, and 99.5% by 7 days after a single dose of labeled difluprednate instilled in the right eyes of pigmented rabbits.
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Preclinical pharmacokinetic and toxicity studies have established that difluprednate ophthalmic emulsion 0.05% given 4 times a day is not toxic to the eye.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Difluprednate can be increased when it is combined with Abametapir. Acarbose The risk or severity of hyperglycemia can be increased when Difluprednate is combined with Acarbose. Acetohexamide The risk or severity of hyperglycemia can be increased when Difluprednate is combined with Acetohexamide. Acetyldigitoxin The risk or severity of adverse effects can be increased when Difluprednate is combined with Acetyldigitoxin. Albiglutide The risk or severity of hyperglycemia can be increased when Difluprednate is combined with Albiglutide. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Durezol Emulsion 0.5 mg/1mL Ophthalmic ALCON LABORATORIES, INC. 2011-01-25 2023-08-31 US 
Durezol Emulsion 0.05 % w/v Ophthalmic Novartis 2014-02-19 Not applicable Canada 
Durezol Emulsion 0.5 mg/1mL Ophthalmic Physicians Total Care, Inc. 2011-08-29 Not applicable US Durezol Emulsion 0.5 mg/1mL Ophthalmic Novartis Farma S.P.A. 2011-01-25 Not applicable US Durezol Emulsion 0.5 mg/1mL Ophthalmic Sirion Therapeutics, Inc. 2008-09-01 2010-06-24 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Difluprednate Emulsion 0.5 mg/1mL Ophthalmic Amneal Pharmaceuticals NY LLC 2021-11-18 Not applicable US Difluprednate Emulsion 0.5 mg/1mL Ophthalmic Exelan Pharmaceuticals Inc. 2021-12-10 Not applicable US Difluprednate Emulsion 0.5 mg/1mL Ophthalmic Cipla USA Inc. 2021-08-09 Not applicable US Difluprednate Ophthalmic Emulsion 0.5 mg/1mL Ophthalmic Sandoz S.P.A. 2013-05-15 Not applicable US Difluprednate Ophthalmic Emulsion Emulsion 0.5 mg/1mL Ophthalmic Dr. Reddy's Laboratories Limited 2022-12-25 Not applicable US
Categories
- ATC Codes
- S01BA16 — Difluprednate
- S01BA — Corticosteroids, plain
- S01B — ANTIINFLAMMATORY AGENTS
- S01 — OPHTHALMOLOGICALS
- S — SENSORY ORGANS
- Drug Categories
- Adrenal Cortex Hormones
- Anti-Inflammatory Agents
- Corticosteroids
- Corticosteroids, Dermatological Preparations
- Corticosteroids, Potent (Group III)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Dermatologicals
- Fused-Ring Compounds
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Immunosuppressive Agents
- Ophthalmologicals
- Pregnadienes
- Pregnadienetriols
- Pregnanes
- Sensory Organs
- Steroids
- Steroids, Fluorinated
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Pregnane steroids
- Direct Parent
- Gluco/mineralocorticoids, progestogins and derivatives
- Alternative Parents
- Steroid esters / 20-oxosteroids / 11-beta-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Alpha-acyloxy ketones / Dicarboxylic acids and derivatives / Cyclic ketones / Cyclic alcohols and derivatives show 7 more
- Substituents
- 11-beta-hydroxysteroid / 11-hydroxysteroid / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 6-halo-steroid / 9-halo-steroid / Alcohol / Aliphatic homopolycyclic compound / Alkyl fluoride show 24 more
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- butyrate ester, corticosteroid hormone (CHEBI:31485)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- S8A06QG2QE
- CAS number
- 23674-86-4
- InChI Key
- WYQPLTPSGFELIB-JTQPXKBDSA-N
- InChI
- 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
- IUPAC Name
- (1R,3aS,3bS,5S,9aS,9bR,10S,11aS)-1-[2-(acetyloxy)acetyl]-5,9b-difluoro-10-hydroxy-9a,11a-dimethyl-7-oxo-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-1-yl butanoate
- SMILES
- [H][C@@]12CC[C@](OC(=O)CCC)(C(=O)COC(C)=O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C
References
- Synthesis Reference
Ercoli, A. and Gardi, R.; U.S. Patent 3,780,177; December 18,1973; assigned to Warner-Lambert Co.
- General References
- Korenfeld MS, Silverstein SM, Cooke DL, Vogel R, Crockett RS: Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain. J Cataract Refract Surg. 2009 Jan;35(1):26-34. doi: 10.1016/j.jcrs.2008.09.024. [Article]
- Jamal KN, Callanan DG: The role of difluprednate ophthalmic emulsion in clinical practice. Clin Ophthalmol. 2009;3:381-90. Epub 2009 Jun 29. [Article]
- Morton KD, Van de Kar LD, Brownfield MS, Bethea CL: Neuronal cell bodies in the hypothalamic paraventricular nucleus mediate stress-induced renin and corticosterone secretion. Neuroendocrinology. 1989 Jul;50(1):73-80. [Article]
- External Links
- Human Metabolome Database
- HMDB0061149
- KEGG Drug
- D01266
- KEGG Compound
- C12695
- PubChem Compound
- 443936
- PubChem Substance
- 99443292
- ChemSpider
- 391990
- 23043
- ChEBI
- 31485
- ChEMBL
- CHEMBL1201749
- ZINC
- ZINC000004212945
- PharmGKB
- PA165958405
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Difluprednate
- FDA label
- Download (149 KB)
- MSDS
- Download (129 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Completed Treatment Cataracts 1 somestatus stop reason just information to hide 4 Completed Treatment Cataracts / Corneal Edema / Retinal Structural Change, Deposit and Degeneration / Visual Acuity Reduced Transiently 1 somestatus stop reason just information to hide 4 Recruiting Treatment Anterior Uveitis (AU) 1 somestatus stop reason just information to hide 4 Terminated Treatment Cataracts 1 somestatus stop reason just information to hide 4 Terminated Treatment Macular Edema / Uveitis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Emulsion Ophthalmic 0.50 mg Ointment 20 g Emulsion Ophthalmic 0.05 % w/v Emulsion Ophthalmic 0.5 mg/1mL Solution Ophthalmic 0.5 mg Solution Ophthalmic; Topical 0.5 mg Ointment 0.05 % - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6114319 Yes 2000-09-05 2019-11-18 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 191-194 Ercoli, A. and Gardi, R.; U.S. Patent 3,780,177; December 18,1973; assigned to Warner-Lambert Co. - Predicted Properties
Property Value Source Water Solubility 0.0097 mg/mL ALOGPS logP 3.28 ALOGPS logP 3 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 13.6 Chemaxon pKa (Strongest Basic) -3.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 106.97 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 125.38 m3·mol-1 Chemaxon Polarizability 51.45 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9904 Blood Brain Barrier + 0.9908 Caco-2 permeable + 0.6127 P-glycoprotein substrate Substrate 0.7679 P-glycoprotein inhibitor I Inhibitor 0.6413 P-glycoprotein inhibitor II Non-inhibitor 0.789 Renal organic cation transporter Non-inhibitor 0.8044 CYP450 2C9 substrate Non-substrate 0.8882 CYP450 2D6 substrate Non-substrate 0.9152 CYP450 3A4 substrate Substrate 0.7641 CYP450 1A2 substrate Non-inhibitor 0.9138 CYP450 2C9 inhibitor Non-inhibitor 0.911 CYP450 2D6 inhibitor Non-inhibitor 0.8162 CYP450 2C19 inhibitor Non-inhibitor 0.94 CYP450 3A4 inhibitor Non-inhibitor 0.7263 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9014 Ames test Non AMES toxic 0.9326 Carcinogenicity Non-carcinogens 0.9242 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.1368 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9677 hERG inhibition (predictor II) Non-inhibitor 0.5493
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 229.7903609 predictedDarkChem Lite v0.1.0 [M-H]- 227.3684609 predictedDarkChem Lite v0.1.0 [M-H]- 215.4412 predictedDeepCCS 1.0 (2019) [M-H]- 229.7903609 predictedDarkChem Lite v0.1.0 [M-H]- 227.3684609 predictedDarkChem Lite v0.1.0 [M-H]- 215.4412 predictedDeepCCS 1.0 (2019) [M+H]+ 227.8008609 predictedDarkChem Lite v0.1.0 [M+H]+ 226.4771609 predictedDarkChem Lite v0.1.0 [M+H]+ 217.31184 predictedDeepCCS 1.0 (2019) [M+H]+ 227.8008609 predictedDarkChem Lite v0.1.0 [M+H]+ 226.4771609 predictedDarkChem Lite v0.1.0 [M+H]+ 217.31184 predictedDeepCCS 1.0 (2019) [M+Na]+ 229.3034609 predictedDarkChem Lite v0.1.0 [M+Na]+ 227.5840609 predictedDarkChem Lite v0.1.0 [M+Na]+ 223.39073 predictedDeepCCS 1.0 (2019) [M+Na]+ 229.3034609 predictedDarkChem Lite v0.1.0 [M+Na]+ 227.5840609 predictedDarkChem Lite v0.1.0 [M+Na]+ 223.39073 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). 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 (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity)
- Specific Function
- core promoter sequence-specific DNA binding
- Gene Name
- NR3C1
- Uniprot ID
- P04150
- Uniprot Name
- Glucocorticoid receptor
- Molecular Weight
- 85658.57 Da
References
- Jamal KN, Callanan DG: The role of difluprednate ophthalmic emulsion in clinical practice. Clin Ophthalmol. 2009;3:381-90. Epub 2009 Jun 29. [Article]
- Tajika T, Takahashi H, Sakai Y, Fujii H, Isowaki A, Sakaki H: Metabolic profiles of difluprednate in rabbit ocular tissues after instillation of difluprednate ophthalmic emulsion. Xenobiotica. 2010 Aug;40(8):569-77. doi: 10.3109/00498254.2010.490308. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity)
- Specific Function
- cadherin binding involved in cell-cell adhesion
- Gene Name
- ANXA1
- Uniprot ID
- P04083
- Uniprot Name
- Annexin A1
- Molecular Weight
- 38713.855 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Cerny MA: Prevalence of Non-Cytochrome P450-Mediated Metabolism in Food and Drug Administration-Approved Oral and Intravenous Drugs: 2006-2015. Drug Metab Dispos. 2016 Aug;44(8):1246-52. doi: 10.1124/dmd.116.070763. Epub 2016 Apr 15. [Article]
Drug created at September 14, 2010 16:21 / Updated at August 26, 2024 19:24