Dmgiaanic Difluprednate (DB0678l)
`
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`ldermflcation
`
`Name
`
`Difluprednate
`
`Accession Number DB06781
`
`Type
`
`Groups
`
`Description
`
`Structure
`
`Small Molecule
`
`Approved
`
`Ditluprednate is a topil corticosteroid indicated for the trtrnent of infammation and pain associated with ocular surgery. It is a
`butyrate ester of 6(a), 9(a)—difluoro prednisolone acetate. Difluprednate is abbreviated DFBA, or difluoroprednisolone butyrate
`acetate. It is indicated for treatment of endogenous anterior uveiti.
`
`
`
`13 MOL SDF PDB SMILES incni
`
`sV"°"Vm3
`
`Show 10
`
`entries
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`Search
`
`Synonym
`
`DFBA
`
`Difluoroprednisolone butyrate acetate
`
`Durezol
`
`Showing 1 to 3 of 3 entries
`
`: Language
`
`Not Available
`
`Not Available
`
`Not Available
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`code
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`Not Available
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`Not Available
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`Not Available
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`Name
`
`: Dosage
`
`Strength
`
`Route
`
`Labeller
`
`Marketing Stan
`
`Marketing End
`
`Durezol
`
`emulsion
`
`.5 mgImL
`
`ophthalmic
`
`Alcon Laboratories, Inc.
`
`2011-01-25
`
`Not Available
`
`Durezol
`
`emulsion
`
`.5 mgImL
`
`ophthalmic
`
`Physicians Total Care,
`Inc.
`
`2011-08-29
`
`Not Available
`
`Durezol
`
`emulsion
`
`0.05 '56
`
`ophthalmic
`
`Alcon Canada Inc
`
`Not Available
`
`Not Available
`
`Showing 1 to 3 of 3 entries
`Not Available
`
`Generic
`
`Prescription
`Products
`
`Over the Counter
`Products
`
`Not Available
`
`International
`Brands
`
`Not Available
`
`Brand mixtures
`
`Not Available
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`imp://wwwaxugbankca/drugs/DBo67s1[7r21r2o151o:31:26AM]
`
`SEN J U_M |'|'SU B |SH| 2029
`
`

`
`DrugBank: Difluprednate (DB06781)
`
`Salts
`
`Categories
`
`Not Available
`
`Anti-Inflammatory Agents
`Glucocorticoids
`Corticosteroids
`
`CAS number
`
`23674-86-4
`
`Weight
`
`Average: 508.5515
`Monoisotopic: 508.227259852
`
`Chemical Formula
`
`C H F O
`27 34 2 7
`
`InChI Key
`
`InChI
`
`IUPAC Name
`
`SMILES
`
`Taxonomy
`
`Description
`
`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
`
`(1R,2S,8S,10S,11S,14R,15S,17S)-14-[2-(acetyloxy)acetyl]-1,8-difluoro-17-hydroxy-2,15-dimethyl-5-
`oxotetracyclo[8.7.0.0²,
`.0¹¹,¹
`]heptadeca-3,6-dien-14-yl butanoate
`
`[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
`
`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-l ke molecules
`
`
`Class
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`Sub Class
`
`Steroids and steroid derivatives
`
`
`Pregnane steroids
`
`
`
`Direct Parent
`
`Gluco/mineralocorticoids, progestogins and derivatives
`
`
`Alternative Parents
`
`Steroid esters
`
`20-oxosteroids
`
`Halogenated steroids
`
`3-oxo delta-1,4-steroids
`11-beta-hydroxysteroids
`Delta-1,4-steroids
`
`Alpha-acyloxy ketones
`Acetate salts
`
`Secondary alcohols
`
`Fluorohydrins
`Cyclic ketones
`Cyclic alcohols and derivatives
`Carboxylic acid esters
`
`Monocarboxylic acids and derivatives
`Organofluorides
`
`Hydrocarbon derivatives
`Alkyl fluorides
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Substituents
`
`Progestogin-skeleton
`Steroid ester
`20-oxosteroid
`11-hydroxysteroid
`11-beta-hydroxysteroid
`Oxosteroid
`Hydroxysteroid
`Halo-steroid
`6-halo-steroid
`9-halo-steroid
`3-oxosteroid
`
`http://www drugbank ca/drugs/DB06781[7/21/2015 10:31:26 AM]
`
`

`
`Dmgiaanic Difluprednate (0305731)
`
`o 3-oxo—de|ta-1,4-steroid
`o De|ta—1,4-steroid
`o Alphaacyloxy ketone
`. Acetate salt
`
`a Cyclic alcohol
`0 Cyclic ketone
`0 Secondary alcohol
`- Ketone
`
`9 Halohydrin
`- Fluorohydrin
`o Caiboxylic acid ester
`0 Moriocarboxylic acidorderivatives
`- Caiboxylic acid derivative
`0 Hydrocarbon derivative
`o Organooxygen compound
`0 Organofluoride
`o ()rganohalogen compound
`a Carbonyl group
`o Alkyl halide
`. Alkyllluoride
`0 Alcohol
`
`0 Aliphatic homopolycyclic compound
`
`Molecular
`Framework
`
`External
`
`Descriptors
`
`Aliphatic homopolycyclic compounds
`
`Not Available
`
`
`Pharmac:c:logv
`Indication
`For the treatment of inflammation and pain associated with ocular surgery.
`
`Pharmacodynamics
`
`Difluprednate is a corticosteroid used as an anti-inflarnmatory steroidal dnig used primarily in ocular surgery.
`
`Mechanism of
`action
`
`Absorption
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`Volume of
`distribution
`
`Protein binding
`
`Metabolism
`
`Route of
`elimination
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`Half life
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`Clearance
`
`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 prostaglandiris and leukotrienes by inhibiting the
`relse of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by
`phospholipase A2.
`
`Difluprednate penetrates the corneal epithelium rapidly and effectively. Low systemic absorption.
`
`Not Available
`
`Not Available
`
`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 hydroxytluoroprednisolorie butyrate (HFB), which limits
`systemic exposure to the active compound.
`
`Substrate
`
`Enzymes
`
`Product
`
`Difluprednate
`
`D
`Not Available
`
`difluoroprednisolone butyrate
`
`Difluprednate
`
`D
`Not Available
`
`Hydroxyfluoroprednisolone butyrate (HFB)
`
`78.5% of radioactivity was excreted aftert 24 hours, and 99.5% by 7 days after a single dose of labeled ditluprednate instilled in
`the right eyes of pigmented rabbits.
`
`Not Available
`
`Not Available
`
`littpz/lwwwdrugbankcaldrugs/DB06'l81[7f2lI20lS io31:25AM]
`
`

`
`DtugBank Difluprulnate (DB0678l)
`
`Toxicity
`
`Preclinical phannacokinetic and toxicity studies have established that dilluprednate ophthalmic emulsion 0.05% given 4 times a
`day is not toxic to the eye.
`
`Affected organisms
`
`o Humans and other mammals
`
`Pathways
`
`SNP Mediated
`Effects
`
`Not Available
`
`Not Available
`
`SNP Mediated
`
`Not Available
`
`Adverse Drug
`Reactions
`
`Predicted ADMET
`features
`
`Property
`
`Human Intestinal Absorption
`
`Blood Brain Barrier
`
`Caco-2 penneable
`
`P—glycoprotein substrate
`
`P—glycoprotein inh bitor I
`
`Pglycoprotein inh bitor ll
`
`Renal organic cation transporter
`
`CYP450 2C9 substrate
`
`CYP450 2D6 substrate
`
`CYP450 3A4 substrate
`
`CYP450 1A2 substrate
`
`CYP450 2C9 substrate
`
`Value
`
`+
`
`+
`
`+
`
`Substrate
`
`Inhibitor
`
`Noninhibitor
`
`Non-inhibitor
`
`Non-substrate
`
`Non-substrate
`
`Substrate
`
`Non-inhibitor
`
`Non-inhibitor
`
`Probability
`
`0.9904
`
`0.9908
`
`0.6127
`
`0.7679
`
`0.6413
`
`0.789
`
`0.8044
`
`0.8882
`
`0.9152
`
`0.7641
`
`0.9138
`
`0.911
`
`CYP450 2D6 substrate
`
`CYP450 2C19 substrate
`
`CYP450 3A4 substrate
`
`Noninhibitor
`
`Non-inhibitor
`
`Non-inhibitor
`
`CYP450 inhibitory promiscuity
`
`Low CYP Inhibitory Promiscuity
`
`Ames test
`
`Carcinogenicity
`
`Biodegradation
`
`Rat acute toxicity
`
`hERG inh bition (predictor I)
`
`hERG inh bition (predictor II)
`
`Non AMES toxic
`
`Non-carcinogens
`
`Not ready biodegradable
`
`2.1368 LD50, mollkg
`
`Weak inhibitor
`
`Non-inhibitor
`
`0.8162
`
`0.94
`
`0.7263
`
`0.9014
`
`0.9326
`
`0.9242
`
`1.0
`
`Not applicable
`
`0.9677
`
`0.5493
`
`F’harmacoecoi‘iomIcs
`
`Manufacturers
`
`Not Available
`
`Packagers
`
`Not Available
`
`D°sa9° forms
`
`Show 10
`
`entries
`
`Form
`
`Emulsion
`
`Emulsion
`
`Showing 1 to 2 of 2 entries
`
`’ Route
`
`ophthalmic
`
`ophthalmic
`
`httpzl/www drugbank caldrugs/DB06781[7l21f).0l5 l0:31:26AM]
`
`Search
`
`Strength
`
`.5 mgImL
`
`0.05 %
`
`Previous
`
`Next
`
`

`
`DrugBank: Difluprednate (DB06781)
`
`Prices
`
`Patents
`
`Properties
`
`State
`
`Experimental
` Properties
`
`Predicted
` Properties
`
`Not Available
`
`Not Available
`
`Solid
`
`Property
`
`Value
`
`Source
`
`melting point
`
`191-194 Ercoli, A. and Gardi, R.; U.S. Patent 3,780,177; December 18,1973; assigned to Warner-Lambert Co.
`
`Property
`
`Water Solubility
`
`logP
`
`logP
`
`logS
`
`pKa (Strongest Acidic)
`
`pKa (Strongest Basic)
`
`Physiological Charge
`
`Hydrogen Acceptor Count
`
`Hydrogen Donor Count
`
`Polar Surface Area
`
`Rotatable Bond Count
`
`Refractivity
`
`Polarizability
`
`Number of Rings
`
`Bioavailability
`
`Rule of Five
`
`Ghose Filter
`
`Veber's Rule
`
`MDDR-l ke Rule
`
`Value
`
`0.0097 mg/mL
`
`3.28
`
`3
`
`-4.7
`
`13.55
`
`-3.4
`
`0
`
`5
`
`1
`
`106.97 Å
`
`2
`
`8
`
`3
`125.38 m ·mol
`
`-1
`
`51.46 Å
`
`3
`
`4
`
`1
`
`Yes
`
`Yes
`
`Yes
`
`Yes
`
`Source
`
`ALOGPS
`
`ALOGPS
`
`ChemAxon
`
`ALOGPS
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`ChemAxon
`
`Spectra
`
`Mass Spec (NIST)
`
`Not Available
`
`Spectra
`
`References
`
`Synthesis
` Reference
`
`General Reference
`
`Not Available
`
`Ercoli, A. and Gardi, R.; U.S. Patent 3,780,177; December 18,1973; assigned to Warner-Lambert Co.
`
`1. 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. Pubmed
`2. Jamal KN, Callanan DG: The role of difluprednate ophthalmic emulsion in clinical practice. Clin Ophthalmol. 2009;3:381-90.
` Epub 2009 Jun 29. Pubmed
`3. https://online.epocrates.com/u/10a4844/Durezol
`4. 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. Pubmed
`
`External Links
`
`Resource
`
`Link
`
`KEGG Drug D01266
`
` 
`
`PubChem
` Compound
`
`443936
`
`http://www drugbank ca/drugs/DB06781[7/21/2015 10:31:26 AM]
`
`

`
`Dmgnanr Difluptednate (DB0678l)
`
`Pubchem
`Substance
`
`99443292
`
`Chemspider 391990
`
`PhannGKB PA165958405
`
`Rxl_ist
`
`http://www_rx|ist_cornldurezol-drug.htm
`
`Drugs.com
`
`http://wwwidrugs.com/durezo|.htmI
`
`PDRhealth
`
`http://wvvw.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFi|eName=dur1999.html&contentName=Durezol&contentld=269
`
`W kipedia
`
`Difluprednate
`
`ATC Codes
`
`D07AC19
`D — DERMATOLOGICALS
`
`D07 — CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS
`D07A — CORTICOSTEROIDS, PLAIN
`D07AC — Corticosteroids, potent (group III)
`
`AHFS Codes
`
`Not Available
`
`PDB Entries
`
`Not Available
`
`FDA label
`
`Download (149 KB)
`
`MSDS
`
`Download (129 KB)
`
`|r‘nteract|«::>n5
`
`Drug Interactions
`
`Show 10
`
`entries
`
`Drug
`
`Aldesleukin
`
`*
`
`Deferasirox
`
`May diminish the antineoplastic effect of Aldesleukin. Exceptions: Beclomethasone (Nasal); Budesonide
`(Nasal); Ciclesonide (Nasal); Desonide; Dexamethasone (Ophthalmic); Dilluprednate; Flunisolide (Nasal);
`Fluocinolone (Ophthalmic); Fluticasone (Nasal); Loteprednol; Mornetasone (Nasal); PrednisoLONE
`(Ophthalmic); Triamcinolone (Nasal); Triamcinolone (Ophthalmic).
`
`May enhance the adverseltoxic effect of Deferasirox. Specifically, the risk for GI ulcerationfinitation or GI
`bleeding may be increased. Exceptions: Beclomethasone (Nasal); Budesonide (Nasal); Ciclesonide
`(Nasal); Desonide; Dexamethasone (Ophthalmic); Dilluprednate; Flunisolide (Nasal); Fluocinolone
`(Ophthalmic); Fluticasone (Nasal); Loteprednol; Mometasone (Nasal); PrednisoLONE (Ophthalmic);
`Tliamcinolone (Nasal); Triamcinolone (Ophthalmic).
`
`Hyaluronidase
`
`May diminish the therapeutic effect of Hyaluronidase.
`
`Telaprevir
`
`May decrease the semm concentration of Telaprevir. Telaprevir may increase the semm concentration of
`Corticosteroids.
`
`Showing 1 to 4 of 4 entries
`
`Food Interactions
`
`Not Available
`
`Previous
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`Next
`
`Targets
`
`
`1. Glucocorticoid receptor
`
`Kind: protein
`
`Organism: Human
`
`Phamlaoologil action:
`
`Acrwns:
`
`Components
`
`map://wwwaxugbanku/azugs/DBo67s1[7/21r2o15 10:31:26AM]
`
`UniProt ID
`
`Details
`
`

`
`Dzugnanic Difluptudn:te(DB0678l)
`
`Gluoocortiooid receptor
`
`P04150
`
`Dem;
`
`References:
`
`1. Jamal KN, callanan DG: The role of dilliplediate ophthalnic emulsion in clinic: practice. Clin Ophlhalnol. 2009;3:381-90. Epub 2009 Jim 29. Pubmed
`2 Tajika T, Takahashi H, saka‘ Y, Fiji H, Isowaki A, sakaki H: Metabolic profiles of difluprednate ‘It rabbit ocu:-I tissues after instiation of diflupremate
`ophthdmic emilsion_ Xenobiotica_ 2010 Aug;40(8):569-77. Pubmed
`
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`Dmg created on September 14, 2010 10:21 I Updated on Apri 14, 2014 12:57
`
`-
`
`W .
`This project is supported by the Canadian Institutes of Health Research (award
`) 59"’
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