DICLOFENAC

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H11Cl2NO2
Molecular Weight	296.149
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC1=C(NC2=C(Cl)C=CC=C2Cl)C=CC=C1

InChI

InChIKey=DCOPUUMXTXDBNB-UHFFFAOYSA-N

InChI=1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)

HIDE SMILES / InChI

Molecular Formula	C14H11Cl2NO2
Molecular Weight	296.149
Charge	0
Count

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

Description
Sources: https://www.drugs.com/pro/diclofenac.html
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25963327 | https://www.ncbi.nlm.nih.gov/pubmed/20470236 | http://www.pharmaceutical-journal.com/news-and-analysis/news/diclofenac-a-useful-drug-that-may-now-be-entering-its-twilight-years/11121261.article

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. In addition diclofenac can inhibit the thromboxane-prostanoid receptor, affect arachidonic acid release and uptake, inhibit lipoxygenase enzymes, and activate the nitric oxide-cGMP antinociceptive pathway. Other novel mechanisms of action may include the inhibition of substrate P, inhibition of peroxisome proliferator activated receptor gamma (PPARgamma), blockage of acid-sensing ion channels, alteration of interleukin-6 production, and inhibition of N-methyl-D-aspartate (NMDA) receptor hyperalgesia. Similar to other NSAIDs, diclofenac is associated with serious dose-dependent gastrointestinal, cardiovascular, and renal adverse effects. Since its introduction in 1973, a number of different diclofenac-containing drug products have been developed with the goal of improving efficacy, tolerability, and patient convenience. Delayed- and extended-release forms of diclofenac sodium were initially developed with the goal of improving the safety profile of diclofenac and providing convenient, once-daily dosing for the treatment of patients with chronic pain. New drug products consisting of diclofenac potassium salt were associated with faster absorption and rapid onset of pain relief. These include diclofenac potassium immediate-release tablets, diclofenac potassium liquid-filled soft gel capsules, and diclofenac potassium powder for oral solution. The advent of topical formulations of diclofenac enabled local treatment of pain and inflammation while minimizing systemic absorption of diclofenac. SoluMatrix diclofenac, consisting of submicron particles of diclofenac free acid and a proprietary combination of excipients, was developed to provide analgesic efficacy at reduced doses associated with lower systemic absorption. The drug's likely impact on the Asian vulture population was widely reported. The dramatic mortality was attributed largely to renal failure caused by exposure to diclofenac in livestock carcasses on which the birds fed. Although not the most endearing species, vultures are important environmental scavengers and, since veterinary use of diclofenac was stopped in the region in 2006, the decline in vulture numbers has slowed.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7980626 \| https://www.ncbi.nlm.nih.gov/pubmed/9444611 \| https://www.ncbi.nlm.nih.gov/pubmed/11804398 \| https://www.ncbi.nlm.nih.gov/pubmed/10381057 \| https://www.ncbi.nlm.nih.gov/pubmed/9650852	Inhibitor 8297		0.97 nM [IC50]
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9444611 \| https://www.ncbi.nlm.nih.gov/pubmed/11804398 \| https://www.ncbi.nlm.nih.gov/pubmed/10381057 \| https://www.ncbi.nlm.nih.gov/pubmed/9650852	Inhibitor 8297		0.037 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 316 Sources: https://www.drugs.com/pro/diclofenac.html	Primary		Approved 8429	DICLOFENAC SODIUM Approved Use Diclofenac Sodium Extended-release Tablets are indicated: •For relief of the signs and symptoms of osteoarthritis •For relief of the signs and symptoms of rheumatoid arthritis
Osteoarthritis 157 Sources: https://www.drugs.com/pro/diclofenac.html	Primary		Approved 8429	DICLOFENAC SODIUM Approved Use Diclofenac Sodium Extended-release Tablets are indicated: •For relief of the signs and symptoms of osteoarthritis •For relief of the signs and symptoms of rheumatoid arthritis

C_max

Value	Dose	Analyte	Population
902 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19531931	50 mg 3 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DICLOFENAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
302 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19531931	12.5 mg 3 times / day steady-state, oral dose: 12.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DICLOFENAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
749 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19531931	25 mg 3 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DICLOFENAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1208 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19531931	50 mg 3 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DICLOFENAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
319 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19531931	12.5 mg 3 times / day steady-state, oral dose: 12.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DICLOFENAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
609 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19531931	25 mg 3 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DICLOFENAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
1.64 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19531931	50 mg 3 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DICLOFENAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19531931	12.5 mg 3 times / day steady-state, oral dose: 12.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DICLOFENAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.87 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19531931	25 mg 3 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DICLOFENAC plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
2.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019201s038lbl.pdf	unknown, oral	DICLOFENAC serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019201s038lbl.pdf	unknown, oral		DICLOFENAC serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
75 mg/mL single, intravenous Dose: 75 mg/mL Route: intravenous Route: single Dose: 75 mg/mL Sources: https://pubmed.ncbi.nlm.nih.gov/31077065/	healthy, 18 - 53 years Health Status: healthy Age Group: 18 - 53 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/31077065/	Sources: https://pubmed.ncbi.nlm.nih.gov/31077065/
50 mg single, oral Dose: 50 mg Route: oral Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31131893/	healthy, 21-51 years n = 24 Health Status: healthy Age Group: 21-51 years Sex: M+F Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/31131893/	Other AEs: Nephrotoxicity... Other AEs: Nephrotoxicity Sources: https://pubmed.ncbi.nlm.nih.gov/31131893/
500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf	unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf	Disc. AE: Drowsiness, Lethargy... AEs leading to discontinuation/dose reduction: Drowsiness Lethargy Nausea Vomiting Epigastric pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf

AEs

AE	Significance	Dose	Population
Nephrotoxicity		50 mg single, oral Dose: 50 mg Route: oral Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31131893/	healthy, 21-51 years n = 24 Health Status: healthy Age Group: 21-51 years Sex: M+F Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/31131893/
Drowsiness	Disc. AE	500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf	unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf
Epigastric pain	Disc. AE	500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf	unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf
Lethargy	Disc. AE	500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf	unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf
Nausea	Disc. AE	500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf	unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf
Vomiting	Disc. AE	500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf	unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019201s035lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 788 OATP1B3 706 MCT4 9 CYP2C19 1478 CYP1A2 1524 BCRP 699 BSEP 402 UGT1A1 204 UGT1A3 84 UGT1A6 108 UGT1A7 21 UGT1A8 36 UGT1A9 116 UGT1A10 32 UGT2B7 146 UGT2B15 64 UGT2B17 18 MRP1 106 MRP4 204 OAT3 642	UGT1A1 418 UGT1A4 347 UGT1A6 307 UGT1A8 283 UGT1A9 380 UGT2B7 389 UGT2B15 203 OATP1B1 406 CYP1A2 1054 CYP2C19 991 CYP2C18 138 CYP2B6 664 BCRP 561 P-gp 1537 MRP2 205 OAT2 115 OAT1 326 OAT3 339 OAT4 78 OATP2B1 104 MRP3 50 OATP1B3 350

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	moderate	4'-hydroxydiclofenac 8
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no	4'-hydroxydiclofenac 8
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no	4'-hydroxydiclofenac 8
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	strong
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24014644/	weak
MRP1 172	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12835412/	weak
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12835412/	weak
UGT1A9 121	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 11 uM]
UGT1A7 23	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 19 uM]
UGT1A10 41	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 28 uM]
UGT1A1 254	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 52 uM]
UGT1A6 141	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 60 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	yes
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	yes
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	yes	4'-hydroxydiclofenac 8
MCT4 28	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/27236641/	yes
MRP2 475	activator 214 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	yes
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11306713/	yes
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21861202/ \| https://pubmed.ncbi.nlm.nih.gov/21389119/	yes
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21389119/	yes
UGT1A3 93	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT1A8 48	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT2B15 64	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT2B17 20	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT2B7 157	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes

Drug as victim

Target	Modality	Activity	Metabolite
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/ \| https://pubmed.ncbi.nlm.nih.gov/12871048/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019201s039s040lbl.pdf	major
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	minor
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	minor
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	minor
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	moderate
MRP2 205	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/ \| https://pubmed.ncbi.nlm.nih.gov/26714763/	no
MRP3 50	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OAT3 339	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OAT4 78	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OATP1B1 406	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21389119/ \| https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OATP2B1 104	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	no
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	no
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	no
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	yes
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10449188/	yes
CYP2C18 138	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10449188/	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10449188/	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12871048/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019201s039s040lbl.pdf	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12871048/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019201s039s040lbl.pdf	yes
MRP2 205	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
MRP3 50	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT2 115	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes
OAT2 115	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT3 339	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT4 78	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OATP1B1 406	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OATP2B1 104	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/23578606/		hydroxypropyl-β-cyclodextrin-diclofenac 8

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:47381	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:47381
ChemicalBook	CB5225367	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5225367
MolPort	MolPort-000-003-072	https://www.molport.com/shop/molecule-link/MolPort-000-003-072
ZINC	ZINC000000001281	http://zinc15.docking.org/substances/ZINC000000001281
eMolecules	901753	https://www.emolecules.com/cgi-bin/more?vid=901753

PubMed

Title	Date	PubMed
Nimesulide, a balanced drug for the treatment of osteoarthritis.	2001	11296545
Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six weeks treatment in patients with osteoarthritis.	2001	11252687
Celecoxib versus diclofenac in the management of osteoarthritis of the knee.	2001	11252686
Review: uveitis and immunosuppressive drugs.	2001 Apr	11324985
Cataflam-induced esophageal ulceration.	2001 Apr	11316193
Anti-inflammatory drugs. IX. Hydrated diethylammonium (2-(2,6-dichlorophenylamino)phenyl)acetate (HDEA.D.H2O).	2001 Apr	11313587
Efficacy of peripheral morphine analgesia in inflamed, non-inflamed and perineural tissue of dental surgery patients.	2001 Apr	11312048
Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs.	2001 Apr	11311634
Influence of electrical and chemical factors on transdermal iontophoretic delivery of three diclofenac salts.	2001 Apr	11305601
The role of matrix metalloproteinases in ulcerative keratolysis associated with perioperative diclofenac use.	2001 Apr	11297478
Tramadol vs. diclofenac for posttonsillectomy analgesia.	2001 Apr	11296045
Treatment of elderly patients with nabumetone or diclofenac: gastrointestinal safety profile.	2001 Apr	11276273
The epithelial flap for photorefractive keratectomy.	2001 Apr	11264125
Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors.	2001 Apr	11255075
Equivalence of generic and brand-name ophthalmic products.	2001 Apr 1	11296613
HPLC evaluation of diclofenac in transdermal therapeutic preparations.	2001 Apr 17	11292551
Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system.	2001 Apr 28	11295226
Inhibition of COX in ocular tissues: an in vitro model to identify selective COX-2 inhibitors.	2001 Feb	11322639
Comparative study of diclofenac sodium and paracetamol for treatment of pain after adenotonsillectomy in children.	2001 Feb	11299404
Diclofenac-induced gastric mucosal fluorescence in rats.	2001 Feb	11281183
Determination of diclofenac sodium, flufenamic acid, indomethacin and ketoprofen by LC-APCI-MS.	2001 Feb	11272315
Bioequivalence of two aceclofenac tablet formulations after a single oral dose to healthy male Korean volunteers.	2001 Feb	11270806
When should diclofenac be given in ambulatory surgery: preoperatively or postoperatively?	2001 Feb	11259888
[Concentrations of diclofenac in aqueous humor and in plasma after i.v. injection in 59 patients undergoing cataract surgery--a prospective study].	2001 Feb	11258130
Minocycline inhibits the production of inducible nitric oxide synthase in articular chondrocytes.	2001 Feb	11246672
[Topical administration is better than oral administration].	2001 Feb 1	11234523
Determination of drug residues in water by the combination of liquid chromatography or capillary electrophoresis with electrospray mass spectrometry.	2001 Feb 23	11263577
A comparative experimental study of the effects of diclofenac and ketoprofen on the small-bowel mucosa of canines.	2001 Jan	11271513
Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.	2001 Jan 10	11231885
[Liver damage and nonsteroidal anti-inflammatory drugs: case non-case study in the French Pharmacovigilance Database].	2001 Jan-Feb	11322018
Is diclofenac a valuable CYP2C9 probe in humans?	2001 Jan-Feb	11294368
Analgesic effect of epidural neostigmine after abdominal hysterectomy.	2001 Mar	11331165
Perioperative intravenous flurbiprofen reduces postoperative pain after abdominal hysterectomy.	2001 Mar	11305822
Docetaxel extravasation.	2001 Mar	11305072
[Effect of tobramycin with topical diclofenac on arachidonic acid in endotoxin-induced uveitis].	2001 Mar	11283780
Age-related changes in skin permeability of hydrophilic and lipophilic compounds in rats.	2001 Mar	11265590
An assessment of the clinical efficacy of intranasal desmopressin spray in the treatment of renal colic.	2001 Mar	11251523
Physical incompatibility between atracurium and intravenous diclofenac.	2001 Mar	11251469
Role of the epithelium in opposing H(2)O(2)-induced modulation of acetylcholine-induced contractions in rabbit intrapulmonary bronchiole.	2001 Mar	11250878
Pharmacokinetics of oral diclofenac and acetaminophen in children after surgery.	2001 Mar	11240880
Cytochrome P450 expression and related metabolism in human buccal mucosa.	2001 Mar	11238190
Enhanced disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema by topical timolol and its preservative in early postoperative pseudophakia.	2001 Mar	11231772
Simultaneous quantification of neutral and acidic pharmaceuticals and pesticides at the low-ng/l level in surface and waste water.	2001 Mar 16	11293584
Use of ion-exchange resins to prepare 100 microm-sized microcapsules with prolonged drug-release by the Wurster process.	2001 Mar 23	11274808
Decreased flow-dependent dilation in carotid arteries of tissue kallikrein-knockout mice.	2001 Mar 30	11282893
Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs.	2001 May	11320025
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.	2001 May	11306713
Structure-hepatic disposition relationships for cationic drugs in isolated perfused rat livers: transmembrane exchange and cytoplasmic binding process.	2001 May	11303070
Characterization of rat and human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of diclofenac.	2001 May	11294973
Diclofenac sodium injection sterilized by autoclave and the occurrence of cyclic reaction producing a small amount of impurity.	2001 May	11288099

Patents

Sample Use Guides

In Vivo Use Guide

For topical dosage form (gel): For actinic keratosis using Solaraze® 3% gel: Adults—Apply to affected skin area two times a day. Children—Use and dose must be determined by your doctor. For osteoarthritis of the hands, elbows, or wrists using Voltaren® 1% gel: Adults—Apply 2 grams to the affected skin areas four times a day (a total of 8 grams each day). However, the total dose should not exceed 32 grams per day over all affected joints. Use the enclosed dosing card to measure the appropriate dose. Children—Use and dose must be determined by your doctor. For osteoarthritis of the knees, ankles, or feet using Voltaren® 1% gel: Adults—Apply 4 grams to the affected skin areas four times a day (a total of 16 grams each day). However, the total dose should not exceed 32 grams per day over all affected joints. Use the enclosed dosing card to measure the appropriate dose. Children—Use and dose must be determined by your doctor. For topical dosage form (solution): For osteoarthritis of the knee: Adults—40 drops (10 drops at a time) on each affected knee four times a day. Children—Use and dose must be determined by your doctor. For transdermal dosage form (skin patch): For acute pain: Adults—One patch applied to the painful area two times a day. Children—Use and dose must be determined by your doctor. For oral dosage form (capsules): For acute pain: Adults—18 or 35 milligrams (mg) three times a day. Children—Use and dose must be determined by your doctor. For osteoarthritis: Adults—35 milligrams (mg) three times a day. Children—Use and dose must be determined by your doctor. For oral dosage forms (delayed-release tablets, enteric-coated tablets): For ankylosing spondylitis: Adults—25 milligrams (mg) four times a day, with an extra 25 mg dose at bedtime if necessary. Children—Use and dose must be determined by your doctor. For osteoarthritis: Adults—50 milligrams (mg) two or three times a day, or 75 mg two times a day. Children—Use and dose must be determined by your doctor. For rheumatoid arthritis: Adults—50 milligrams (mg) three or four times a day, or 75 mg two times a day. Children—Use and dose must be determined by your doctor. For oral dosage form (immediate-release tablets): For osteoarthritis: Adults—50 milligrams (mg) two or three times a day. Children—Use and dose must be determined by your doctor. For pain or menstrual cramps: Adults—50 milligrams (mg) three times a day. Your doctor may direct you to take 100 mg for the first dose only. Children—Use and dose must be determined by your doctor. For rheumatoid arthritis: Adults—50 milligrams (mg) three or four times a day. Children—Use and dose must be determined by your doctor. For oral dosage form (solution): For migraine headaches: Adults—One packet (50 milligrams) as a single, one time dose. Children—Use and dose must be determined by your doctor.

Route of Administration: Other

In Vitro Use Guide

Acute (24 h) diclofenac toxicity in a range of (10-1000 μM) concentrations was assesed in primary human hepatocytes. The chronic (9 repeated doses) toxicity at one clinically relevant and another higher concentration (6.4 and 100 μM) was also tested. Acute 24 h assessment revealed toxicity only for the highest tested concentration (1 mM). Upon repeated dose exposure, toxic effects were observed even at a low, clinically relevant concentration (6.4 μM).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:42:54 GMT 2023` Edited by `admin` on `Fri Dec 15 15:42:54 GMT 2023`
Record UNII	144O8QL0L1
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

DICLOFENAC

Official Name

English

Diclofenac [WHO-DD]

Common Name

English

DICLOFENAC [MI]

Common Name

English

DICLOFENAC [VANDF]

Common Name

English

DICLOFENAC FREE ACID

Common Name

English

ACECLOFENAC IMPURITY A [EP IMPURITY]

Common Name

English

DICLOFENAC [HSDB]

Common Name

English

diclofenac [INN]

Common Name

English

DICLOFENAC [ORANGE BOOK]

Common Name

English

LAS-41007

Code

English

LAS41007

Code

English

(2-((2,6-DICHLOROPHENYL)AMINO)PHENYL)ACETIC ACID

Systematic Name

English

DICLOFENAC [MART.]

Common Name

English

BENZENEACETIC ACID, 2-((2,6-DICHLOROPHENYL)AMINO)-

Systematic Name

English

DICLOFENAC [USAN]

Common Name

English

DICLOFENAC ACID

Common Name

English

(O-(2,6-DICHLOROANILINO)PHENYL)ACETIC ACID

Common Name

English

Classification Tree Code System Code

WHO-ATC

M01AB05

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

WHO-ATC

S01BC03

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

WHO-ATC

S01CC01

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

CFR

21 CFR 524.590

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

WHO-ATC

D11AX18

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

WHO-VATC

QD11AX18

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

NDF-RT

N0000175722

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

WHO-ATC

M01AB55

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

LIVERTOX

NBK547953

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

WHO-VATC

QM02AA15

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

WHO-VATC

QS01CC01

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

WHO-ATC

M02AA15

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

WHO-VATC

QM01AB05

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

WHO-VATC

QS01BC03

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

NCI_THESAURUS

C1323

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

Code System Code Type Description

DRUG BANK

DB00586

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

PRIMARY

DRUG CENTRAL

865

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

PRIMARY

HSDB

7234

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

RXCUI

3355

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

RxNorm

INN

3270

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

LACTMED

Diclofenac

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

MESH

D004008

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

DAILYMED

144O8QL0L1

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

PRIMARY

EPA CompTox

DTXSID6022923

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

PRIMARY

CAS

15307-86-5

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

PRIMARY

USAN

AB-122

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

ChEMBL

CHEMBL139

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

PRIMARY

SMS_ID

100000092798

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

FDA UNII

144O8QL0L1

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

WIKIPEDIA

DICLOFENAC

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

MERCK INDEX

m4361

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

Merck Index

EVMPD

SUB07092MIG

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

PRIMARY

ECHA (EC/EINECS)

239-348-5

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

PRIMARY

PUBCHEM

3033

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

CHEBI

47381

Created by admin on Fri Dec 15 15:42:54 GMT 2023 , Edited by admin on Fri Dec 15 15:42:54 GMT 2023

PRIMARY

IUPHAR

2714

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

NCI_THESAURUS

C28985

Created by admin on Fri Dec 15 15:42:55 GMT 2023 , Edited by admin on Fri Dec 15 15:42:55 GMT 2023

PRIMARY

Related Record Type Details


					0M77ZW789J

URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 2B7

METABOLIC ENZYME -> INHIBITOR

Interaction Type:

POTENT


					4HZ67LW8L7

OAT-4

TRANSPORTER -> INHIBITOR


					D8T754TT2I

COX-2

TARGET -> INHIBITOR

Qualification:

IC50

Amount:


					L9DP834D1P

CYTOCHROME P450 2C9

METABOLIC ENZYME -> SUBSTRATE


					E6HDG0QI46

COX-1

TARGET -> INHIBITOR

Qualification:

IC50

Amount:


					PU75M58TSF

DICLOFENAC CALCIUM

SALT/SOLVATE -> PARENT

Amount:


					6TGQ35Z71K

DICLOFENAC DIETHYLAMINE

SALT/SOLVATE -> PARENT

Amount:


					0M77ZW789J

URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 2B7

METABOLIC ENZYME -> SUBSTRATE

Comments:

Highly polymorphic enzyme responsible for differential response. Gene is deleted in 90% of Japanese patients leading to a dose reduction.

Amount:


					ZWJ2Y6JZWY

OAT-3

TRANSPORTER -> INHIBITOR


					I81U7H57XI

OAT-1

TRANSPORTER -> INHIBITOR


					L4D5UA6CB4

DICLOFENAC POTASSIUM

SALT/SOLVATE -> PARENT

Amount:


					QTG126297Q

DICLOFENAC SODIUM

SALT/SOLVATE -> PARENT

Amount:


					X5F8EKL9ZG

DICLOFENAC EPOLAMINE

SALT/SOLVATE -> PARENT

Amount:


					5840721PJZ

OAT-2

TRANSPORTER -> INHIBITOR

Amount:

Related Record Type Details


					6US4Q8M8J7

4',5-DIHYDROXYDICLOFENAC

METABOLITE -> PARENT

Interaction Type:

MINOR

Amount:


					GS38436703

5-HYDROXYDICLOFENAC

METABOLITE -> PARENT

Comments:

CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3'-hydroxy-diclofenac

Interaction Type:

MINOR

Amount:


					FP88H4UEQ3

Diclofenac 2,5-Quinone Imine

METABOLITE TOXIC -> PARENT

Comments:

Bioactivation of DF via 5-hydroxylation might be toxicologically more important than that via 40-hydroxylation, based on the fact that 5-OH-DF and DF-2,5-QI appeared to stimulate immune reactions. Not isolated but inferred from GSH reaction.

Interaction Type:

MINOR

Amount: