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Identification
NameNepafenac
Accession NumberDB06802
TypeSmall Molecule
GroupsApproved
Description

Nepafenac is a non-steroidal anti-inflammatory prodrug (NSAID) usually sold as a prescription eye drop. It is used to treat pain and inflammation associated with cataract surgery.

Structure
Thumb
Synonyms
2-amino-3-Benzoylbenzeneacetamide
AHR 9434
AHR-9434
AL 6515
AL-6515
Amfenac amide
Nepafenaco
Nepafenacum
Nevanac
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ilevrosuspension0.3 %ophthalmicAlcon Canada Inc2014-06-01Not applicableCanada
Ilevrosuspension3 mg/mLophthalmicAlcon Laboratories, Inc.2012-12-20Not applicableUs
Nevanacsuspension/ drops1 mg/mLophthalmicAlcon Laboratories, Inc.2005-09-06Not applicableUs
Nevanacsuspension0.1 %ophthalmicAlcon Canada Inc2008-08-21Not applicableCanada
Nevanacsuspension1 mg/mLophthalmicPhysicians Total Care, Inc.2011-08-31Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0J9L7J6V8C
CAS number78281-72-8
WeightAverage: 254.2839
Monoisotopic: 254.105527702
Chemical FormulaC15H14N2O2
InChI KeyInChIKey=QEFAQIPZVLVERP-UHFFFAOYSA-N
InChI
InChI=1S/C15H14N2O2/c16-13(18)9-11-7-4-8-12(14(11)17)15(19)10-5-2-1-3-6-10/h1-8H,9,17H2,(H2,16,18)
IUPAC Name
2-(2-amino-3-benzoylphenyl)acetamide
SMILES
NC(=O)CC1=CC=CC(C(=O)C2=CC=CC=C2)=C1N
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzophenones. These are organic compounds containing a ketone attached to two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzophenones
Direct ParentBenzophenones
Alternative Parents
Substituents
  • Benzophenone
  • Diphenylmethane
  • Phenylacetamide
  • Acetophenone
  • Substituted aniline
  • Aryl ketone
  • Benzoyl
  • Aniline
  • Primary aromatic amine
  • Vinylogous amide
  • Primary carboxylic acid amide
  • Ketone
  • Carboxamide group
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of pain and inflammation associated with cataract surgery.
PharmacodynamicsLow but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects 2 and 3 hours postdose, respectively, following bilateral topical ocular TID dosing of nepafenac ophthalmic suspension, 0.1%. The mean steady-state Cmax for nepafenac and for amfenac were 0.310 ± 0.104 ng/ml and 0.422 ± 0.121 ng/ml, respectively, following ocular administration.
Mechanism of actionNepafenac is a prodrug. After penetrating the cornea, nepafenac undergoes rapid bioactivation to amfenac, which is a potent NSAID that uniformly inhibits the COX1 and COX2 activity.
Related Articles
AbsorptionNepafenac rapidly cross the cornea (6 times faster than diclofenac in vitro).
Volume of distributionNot Available
Protein bindingAmfenac has high affinity toward serum albumin proteins. In vitro, the percent bound to human albumin and human serum was 95.4% and 99.1% respectively.
Metabolism

Nepafenac (prodrug) is deaminated to amfenac (active compound) in the ciliary body epithelium, retina, and choroid by intraocular hydrolases. Subsequently, amfenac undergoes extensive metabolism to more polar metabolites involving hydroxylation of the aromatic ring leading to glucuronide conjugate formation.

Route of eliminationAfter oral administration of 14C-nepafenac to healthy volunteers, urinary excretion was found to be the major route of radioactivity elimination, accounting for approximately 85% of the dose, while fecal excretion represented approximately 6% of the dose. Nepafenac (prodrug) and amfenac (active compound) were not quantifiable in the urine.
Half lifeNot Available
ClearanceNot Available
ToxicityOcularly applied non-steroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.
Affected organismsNot Available
Pathways
PathwayCategorySMPDB ID
Nepafenac Action PathwayDrug actionSMP00702
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9624
Blood Brain Barrier+0.9918
Caco-2 permeable+0.5581
P-glycoprotein substrateNon-substrate0.7608
P-glycoprotein inhibitor INon-inhibitor0.5471
P-glycoprotein inhibitor IINon-inhibitor0.9209
Renal organic cation transporterNon-inhibitor0.8641
CYP450 2C9 substrateNon-substrate0.8471
CYP450 2D6 substrateNon-substrate0.827
CYP450 3A4 substrateNon-substrate0.6542
CYP450 1A2 substrateInhibitor0.6993
CYP450 2C9 inhibitorInhibitor0.547
CYP450 2D6 inhibitorNon-inhibitor0.882
CYP450 2C19 inhibitorInhibitor0.5714
CYP450 3A4 inhibitorNon-inhibitor0.7118
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7441
Ames testNon AMES toxic0.6193
CarcinogenicityNon-carcinogens0.6932
BiodegradationNot ready biodegradable0.719
Rat acute toxicity2.0064 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9797
hERG inhibition (predictor II)Non-inhibitor0.7681
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Suspensionophthalmic0.3 %
Suspensionophthalmic3 mg/mL
Suspensionophthalmic0.1 %
Suspensionophthalmic1 mg/mL
Suspension/ dropsophthalmic1 mg/mL
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6403609 No1998-07-172018-07-17Us
US7834059 No2007-01-312027-01-31Us
US7947295 No2004-06-082024-06-08Us
US8071648 No2005-12-022025-12-02Us
US8324281 No2005-12-022025-12-02Us
US8921337 No2012-03-312032-03-31Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0197 mg/mLALOGPS
logP1.53ALOGPS
logP2.08ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)15.82ChemAxon
pKa (Strongest Basic)1.83ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area86.18 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity74.46 m3·mol-1ChemAxon
Polarizability26.63 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General References
  1. Gamache DA, Graff G, Brady MT, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy. Inflammation. 2000 Aug;24(4):357-70. [PubMed:10850857 ]
  2. Ke TL, Graff G, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: II. In vitro bioactivation and permeation of external ocular barriers. Inflammation. 2000 Aug;24(4):371-84. [PubMed:10850858 ]
  3. Lane SS, Modi SS, Lehmann RP, Holland EJ: Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery. J Cataract Refract Surg. 2007 Jan;33(1):53-8. [PubMed:17189793 ]
  4. Walters T, Raizman M, Ernest P, Gayton J, Lehmann R: In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. J Cataract Refract Surg. 2007 Sep;33(9):1539-45. [PubMed:17720067 ]
  5. Bucci FA Jr, Waterbury LD: Re: Pharmacokinetics and pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. J Cataract Refract Surg. 2008 Aug;34(8):1226; author reply 1226-7. doi: 10.1016/j.jcrs.2008.05.019. [PubMed:18655957 ]
External Links
ATC CodesS01BC10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (119 KB)
MSDSDownload (58.1 KB)
Interactions
Drug Interactions
Drug
PrednisoloneThe risk or severity of adverse effects can be increased when Nepafenac is combined with Prednisolone.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
References
  1. Gamache DA, Graff G, Brady MT, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy. Inflammation. 2000 Aug;24(4):357-70. [PubMed:10850857 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
References
  1. Gamache DA, Graff G, Brady MT, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy. Inflammation. 2000 Aug;24(4):357-70. [PubMed:10850857 ]
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Drug created on September 14, 2010 10:21 / Updated on August 24, 2016 01:53