NEPAFENAC

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H14N2O2
Molecular Weight	254.2839
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

NC(=O)CC1=C(N)C(=CC=C1)C(=O)C2=CC=CC=C2

InChI

InChIKey=QEFAQIPZVLVERP-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C15H14N2O2
Molecular Weight	254.2839
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Amfenac (AHR 5850) is a non-steroidal anti-inflammatory compound possessing antipyretic and analgesic properties. It is an inhibitor of cyclooxygenases. Amfenac sodium has been on the Japanese market since 1986 (as FENAZOX®, Meiji) in an oral dosage form (50 mg, four-times-daily) indicated for the treatment of pain and inflammation associated with rheumatoid and osteoarthritis and low back pain, as well as the treatment of pain and inflammation following surgery, injury or tooth extraction. Amfenac is an active moiety of nepafenac (amfenac amide), the prodrug has very weak cyclooxygenase inhibitory activity whereas amfenac exhibits more potent cyclooxygenase activity. Nepafenac at a concentration of 0.1% (NEVANAC) was approved for marketing in the US in 2005. Nepafenac is also approved for marketing in the European Union(EU) and Japan as well as over 60 other countries for the treatment of postoperative pain and inflammation associated with cataract surgery.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase-1 127	Inhibitor 8,297	64.3 µM [IC50]
Cyclooxygenase-2 196	Inhibitor 8,297	0.15 µM [IC50]
Cyclooxygenase-1 127	Inhibitor 8,297	0.25 µM [IC50]
Cyclooxygenase-2 196	Inhibitor 8,297	0.15 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cataract 15	Palliative		Approved 8,429	NEVANAC
Pain 614	Primary		Approved 8,429	FENAZOX

C_max

Value	Dose	Analyte	Population
5.62 μg/mL	50 mg single, oral	AMFENAC plasma	Homo sapiens
70.1 ng/mL	1 drop single, ocular	AMFENAC aqueous humor	Homo sapiens
205.3 ng/mL	1 drop single, ocular	NEPAFENAC aqueous humor	Homo sapiens
0.847 ng/mL	1 drop 1 times / day steady-state, ocular	NEPAFENAC plasma	Homo sapiens
0.921 ng/mL	1 drop single, ocular	NEPAFENAC plasma	Homo sapiens
0.847 ng/mL	1 drop 1 times / day steady-state, ocular	NEPAFENAC plasma	Homo sapiens
1.15 ng/mL	1 drop single, ocular	AMFENAC plasma	Homo sapiens
1.13 ng/mL	1 drop 1 times / day steady-state, ocular	AMFENAC plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
6.11 μg × h/mL	50 mg single, oral	AMFENAC plasma	Homo sapiens
178.1 ng × h/mL	1 drop single, ocular	AMFENAC aqueous humor	Homo sapiens
331.1 ng × h/mL	1 drop single, ocular	NEPAFENAC aqueous humor	Homo sapiens
1.57 ng × h/mL	1 drop single, ocular	NEPAFENAC plasma	Homo sapiens
1.43 ng × h/mL	1 drop 1 times / day steady-state, ocular	NEPAFENAC plasma	Homo sapiens
3.6 ng × h/mL	1 drop single, ocular	AMFENAC plasma	Homo sapiens
3.7 ng × h/mL	1 drop 1 times / day steady-state, ocular	AMFENAC plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
1.3 h	50 mg single, oral	AMFENAC plasma	Homo sapiens
0.85 h	1 drop single, ocular	NEPAFENAC plasma	Homo sapiens
0.74 h	1 drop 1 times / day steady-state, ocular	NEPAFENAC plasma	Homo sapiens
5.49 h	1 drop single, ocular	AMFENAC plasma	Homo sapiens
6.26 h	1 drop 1 times / day steady-state, ocular	AMFENAC plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
1 drop 1 times / day multiple, topical Recommended	unhealthy, 68.7+/- 9.08	Disc. AE: Hypersensitivity...
1 drop 1 times / day multiple, topical Recommended	unhealthy	Disc. AE: Bleeding, Healing delayed...
100 mg single, oral Studied dose	healthy

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AEs

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AE	Significance	Dose	Population
Hypersensitivity	0.12% Disc. AE	1 drop 1 times / day multiple, topical Recommended	unhealthy, 68.7+/- 9.08
Bleeding	Disc. AE	1 drop 1 times / day multiple, topical Recommended	unhealthy
Corneal disorder (NOS)	Disc. AE	1 drop 1 times / day multiple, topical Recommended	unhealthy
Healing delayed	Disc. AE	1 drop 1 times / day multiple, topical Recommended	unhealthy
Keratitis	Disc. AE	1 drop 1 times / day multiple, topical Recommended	unhealthy

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587	inhibitor 1,767	inhibitor 1,852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2C19 1,478 CYP2E1 882 P-gp 1,461	CYP 270 P-gp 1,537 UGT enzymes 27

Drug as perpetrator

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Target	Modality	Activity	Metabolite
P-gp 1,650	inhibitor 3,277	inconclusive
P-gp 1,650	inhibitor 3,277	inconclusive	amfenac 4
CYP1A2 1,692	inhibitor 3,277	no
CYP1A2 1,692	inhibitor 3,277	no	amfenac 4
CYP2C19 1,553	inhibitor 3,277	no

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Drug as victim

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Target	Modality	Activity	Metabolite
CYP 270	substrate 3,367	inconclusive	amfenac 4
P-gp 1,537	substrate 3,367	inconclusive
P-gp 1,537	substrate 3,367	inconclusive	amfenac 4
UGT enzymes 27	substrate 3,367	likely
UGT enzymes 27	substrate 3,367	likely	amfenac 4

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:75922	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:75922
ChemicalBook	CB01116872	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB01116872
eMolecules	10510502	https://www.emolecules.com/cgi-bin/more?vid=10510502
MolPort	MolPort-003-987-236	https://www.molport.com/shop/molecule-link/MolPort-003-987-236
Selleck Chemicals	Nepafenac	http://www.selleckchem.com/products/Nepafenac.html

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PubMed

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Title	Date	PubMed
New drugs 06, part II.	2006 Aug	16888514
Nepafenac: a unique nonsteroidal prodrug.	2006 Fall	17060788
Prostaglandin E2 inhibition and aqueous concentration of ketorolac 0.4% (acular LS) and nepafenac 0.1% (nevanac) in patients undergoing phacoemulsification.	2007 Jul	17601444
Double-masked comparison of ketorolac tromethamine 0.4% versus nepafenac sodium 0.1% for postoperative healing rates and pain control in eyes undergoing surface ablation.	2007 Jul	17592313
The effects of a cyclooxygenase-2 (COX-2) expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production.	2007 Nov 27	18042295

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Patents

Sample Use Guides

In Vivo Use Guide

One drop of Nepafenac ophthalmic suspension, 0.3% should be applied to the affected eye one-time-daily beginning 1 day prior to cataract surgery, continued on the day of surgery and through the first 2 weeks of the postoperative period. An additional drop should be administered 30 to 120 minutes prior to surgery.

Route of Administration: Topical

In Vitro Use Guide

Nepafenac exhibited only weak COX-1 inhibitory activity (IC50 = 64.3 uM). However, amfenac, an active metabolite of nepafenac, was a potent inhibitor of COX-1 (IC50 = 0.25 uM) and COX-2 activity (IC50 = 0.15 uM).

Substance Class	Chemical
Record UNII	0J9L7J6V8C
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

NEPAFENAC

Official Name

English

nepafenac [INN]

Common Name

English

Nepafenac [WHO-DD]

Common Name

English

NEPAFENAC [USAN]

Common Name

English

NEPAFENAC [EMA EPAR]

Common Name

English

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Classification Tree

Code System

Code

Enzyme Inhibitors

NDF-RT

N0000000160

Chemical Classes for Pharmacologic Classification

NDF-RT

N0000175721

Established Pharmacologic Class

NDF-RT

N0000175722

Analgesic and Antipyretic

NCI_THESAURUS

C257

Antiinflammatory agents, non-steroids

WHO-VATC

QS01BC10

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Code System

Code

Type

Description

MESH

C414203

PRIMARY

PUBCHEM

151075

PRIMARY

LACTMED

Nepafenac

PRIMARY

CHEBI

75922

PRIMARY

INN

7685

PRIMARY

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Related Record

Type

Details


					28O5C1J38A

AMFENAC

METABOLITE ACTIVE -> PRODRUG

Amount:

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Related Record

Type

Details


					28O5C1J38A

AMFENAC

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount	Parameters
Biological Half-life	PHARMACOKINETIC	1.1 hours [0.4 to 2.1] (average)	SINGLE DOSE

Tmax	PHARMACOKINETIC	0.21 hours [0.17 to 0.37] (average)	SINGLE DOSE

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator