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-2 191 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 8146		0.97 nM [IC50]
Cyclooxygenase-1 125 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 8146		0.037 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 310 Sources: https://www.drugs.com/pro/diclofenac.html	Primary		Approved 8307	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 155 Sources: https://www.drugs.com/pro/diclofenac.html	Primary		Approved 8307	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 1670 inhibitor 1532	substrate 985 inhibitor 1695		inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 770 OATP1B3 691 MCT4 9 CYP2C19 1410 CYP1A2 1463 BCRP 678 BSEP 392 UGT1A1 200 UGT1A3 84 UGT1A6 107 UGT1A7 21 UGT1A8 36 UGT1A9 115 UGT1A10 32 UGT2B7 145 UGT2B15 64 UGT2B17 18 MRP1 106 MRP4 202 OAT3 625	UGT1A1 417 UGT1A4 345 UGT1A6 306 UGT1A8 282 UGT1A9 378 UGT2B7 387 UGT2B15 202 OATP1B1 389 CYP1A2 1013 CYP2C19 955 CYP2C18 138 CYP2B6 648 BCRP 545 P-gp 1491 MRP2 196 OAT2 111 OAT1 314 OAT3 328 OAT4 76 OATP2B1 103 MRP3 50 OATP1B3 333

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2C9 1747	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	moderate	4'-hydroxydiclofenac 8
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no	4'-hydroxydiclofenac 8
CYP3A4 1857	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no
CYP3A4 1857	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no	4'-hydroxydiclofenac 8
CYP2C9 1747	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	strong
BSEP 393	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/24014644/	weak
MRP1 170	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12835412/	weak
MRP4 235	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12835412/	weak
UGT1A9 120	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 11 uM]
UGT1A7 23	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 19 uM]
UGT1A10 41	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 28 uM]
UGT1A1 249	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 52 uM]
UGT1A6 139	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 60 uM]
BCRP 751	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	yes
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	yes
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	yes	4'-hydroxydiclofenac 8
MCT4 28	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/27236641/	yes
MRP2 452	activator 208 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	yes
OAT3 627	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11306713/	yes
OATP1B1 785	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/21861202/ \| https://pubmed.ncbi.nlm.nih.gov/21389119/	yes
OATP1B3 700	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/21389119/	yes
UGT1A3 93	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT1A8 48	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT2B15 64	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT2B17 20	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT2B7 156	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes

Drug as victim

Target	Modality	Activity	Metabolite
UGT2B7 387	substrate 3264 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 306	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	minor
UGT1A9 378	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	minor
UGT2B15 202	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	minor
BCRP 545	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	moderate
MRP2 196	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/ \| https://pubmed.ncbi.nlm.nih.gov/26714763/	no
MRP3 50	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OAT1 314	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OAT3 328	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OAT4 76	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OATP1B1 389	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/21389119/ \| https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OATP2B1 103	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
P-gp 1491	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	no
UGT1A1 417	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	no
UGT1A4 345	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	no
UGT1A8 282	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	no
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	yes
CYP2B6 648	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10449188/	yes
CYP2C18 138	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10449188/	yes
CYP2C19 955	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10449188/	yes
CYP2C9 985	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12871048/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019201s039s040lbl.pdf	yes
CYP3A4 1670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12871048/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019201s039s040lbl.pdf	yes
MRP2 196	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
MRP3 50	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT1 314	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT2 111	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes
OAT2 111	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT3 328	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT4 76	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OATP1B1 389	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OATP1B3 333	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OATP2B1 103	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 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
Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations.	2001	11228592
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
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
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
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
Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo.	2001 Feb	11230360
Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia.	2001 Feb	11220426
Thermographic imaging of postoperative inflammation modified by anti-inflammatory pretreatment.	2001 Feb	11213982
Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2.	2001 Feb	11160644
[Topical administration is better than oral administration].	2001 Feb 1	11234523
Mechanisms of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery.	2001 Feb 2	11166293
Determination of drug residues in water by the combination of liquid chromatography or capillary electrophoresis with electrospray mass spectrometry.	2001 Feb 23	11263577
Micronized ethylcellulose used for designing a directly compressed time-controlled disintegration tablet.	2001 Feb 23	11182202
A comparative experimental study of the effects of diclofenac and ketoprofen on the small-bowel mucosa of canines.	2001 Jan	11271513
Truth and consequences.	2001 Jan	11228628
Truth and consequences.	2001 Jan	11228627
Drug biotransformation by human hepatocytes. In vitro/in vivo metabolism by cells from the same donor.	2001 Jan	11211902
Inadvertent diclofenac rechallenge from generic and non-generic prescribing, leading to liver transplantation for fulminant liver failure.	2001 Jan	11204815
Truth and consequences.	2001 Jan	11200682
Misoprostol therapeutics revisited.	2001 Jan	11191738
Inhibition of the nitrosothiol production of cultured osteoarthritic chondrocytes by rhein, cortisol and diclofenac.	2001 Jan	11178941
Behavioral suppression induced by cannabinoids is due to activation of the arachidonic acid cascade in rats.	2001 Jan 19	11166698
Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin.	2001 Jan 5	11165822
[Liver damage and nonsteroidal anti-inflammatory drugs: case non-case study in the French Pharmacovigilance Database].	2001 Jan-Feb	11322018
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
Age-related changes in skin permeability of hydrophilic and lipophilic compounds in rats.	2001 Mar	11265590
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
In vitro based index of topical anti-inflammatory activity to compare a series of NSAIDs.	2001 Mar	11226820
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

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 16 17:56:52 UTC 2022` Edited by `admin` on `Fri Dec 16 17:56:52 UTC 2022`
Record UNII	144O8QL0L1
Record Status	`Validated (UNII)`
Record Version

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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