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

c1ccc(c(c1)CC(=O)O)Nc2c(cccc2Cl)Cl

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-2 188 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 7709		0.97 nM [IC50]
Cyclooxygenase-1 123 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 7709		0.037 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 294 Sources: https://www.drugs.com/pro/diclofenac.html	Primary		Approved 8003	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 152 Sources: https://www.drugs.com/pro/diclofenac.html	Primary		Approved 8003	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 1603 inhibitor 1461	substrate 944 inhibitor 1605		inhibitor 1480

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 741 OATP1B3 657 MCT4 9 CYP2C19 1324 CYP1A2 1386 BCRP 654 BSEP 378 UGT1A1 191 UGT1A3 82 UGT1A6 103 UGT1A7 20 UGT1A8 33 UGT1A9 113 UGT1A10 29 UGT2B7 142 UGT2B15 60 UGT2B17 17 MRP1 102 MRP4 197 OAT3 591	UGT1A1 396 UGT1A4 331 UGT1A6 290 UGT1A8 267 UGT1A9 360 UGT2B7 365 UGT2B15 192 OATP1B1 369 CYP1A2 971 CYP2C19 911 CYP2C18 143 CYP2B6 616 BCRP 506 P-gp 1399 MRP2 179 OAT2 108 OAT1 293 OAT3 305 OAT4 70 OATP2B1 97 MRP3 46 OATP1B3 319

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2C9 1652	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	moderate	4'-hydroxydiclofenac 8
CYP2C19 1394	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no
CYP2C19 1394	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no	4'-hydroxydiclofenac 8
CYP3A4 1768	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no
CYP3A4 1768	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	no	4'-hydroxydiclofenac 8
CYP2C9 1652	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	strong
BSEP 379	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/24014644/	weak
MRP1 168	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/12835412/	weak
MRP4 229	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/12835412/	weak
UGT1A9 118	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 11 uM]
UGT1A7 22	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 19 uM]
UGT1A10 38	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 28 uM]
UGT1A1 239	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 52 uM]
UGT1A6 135	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Ki 60 uM]
BCRP 723	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	yes
CYP1A2 1532	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	yes
CYP1A2 1532	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	yes	4'-hydroxydiclofenac 8
MCT4 28	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/27236641/	yes
MRP2 436	activator 200 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	yes
OAT3 593	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/11306713/	yes
OATP1B1 756	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/21861202/ \| https://pubmed.ncbi.nlm.nih.gov/21389119/	yes
OATP1B3 666	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/21389119/	yes
UGT1A3 91	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT1A8 45	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT2B15 60	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT2B17 19	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes
UGT2B7 153	inhibitor 3041 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes

Drug as victim

Target	Modality	Activity	Metabolite
UGT2B7 365	substrate 3107 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 290	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	minor
UGT1A9 360	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	minor
UGT2B15 192	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	minor
BCRP 506	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	moderate
MRP2 179	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/ \| https://pubmed.ncbi.nlm.nih.gov/26714763/	no
MRP3 46	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OAT1 293	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OAT3 305	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OAT4 70	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OATP1B1 369	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/21389119/ \| https://pubmed.ncbi.nlm.nih.gov/26714763/	no
OATP2B1 97	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	no
P-gp 1399	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/18845662/	no
UGT1A1 396	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	no
UGT1A4 331	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	no
UGT1A8 267	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/11294973/	no
CYP1A2 971	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/23777257/	yes
CYP2B6 616	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/10449188/	yes
CYP2C18 143	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/10449188/	yes
CYP2C19 911	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/10449188/	yes
CYP2C9 944	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/12871048/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019201s039s040lbl.pdf	yes
CYP3A4 1603	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/12871048/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019201s039s040lbl.pdf	yes
MRP2 179	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
MRP3 46	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT1 293	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT2 108	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes
OAT2 108	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT3 305	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OAT4 70	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OATP1B1 369	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OATP1B3 319	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8
OATP2B1 97	substrate 3107 Sources: https://pubmed.ncbi.nlm.nih.gov/26714763/	yes	diclofenac acyl-β-d-glucuronide 8

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1512	inhibitor 1494 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
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
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
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
Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo.	2001 Feb	11230360
Thermographic imaging of postoperative inflammation modified by anti-inflammatory pretreatment.	2001 Feb	11213982
Tacholiquine inhalation and aspirin-induced asthma.	2001 Feb	11171767
Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2.	2001 Feb	11160644
Effects of anti-inflammatory drugs following cataract extraction.	2001 Feb	11150083
[Topical administration is better than oral administration].	2001 Feb 1	11234523
Translocation of drug particles in HPMC matrix gel layer: effect of drug solubility and influence on release rate.	2001 Feb 23	11182208
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
Effects of diclofenac in the rat tail ischaemia--reperfusion injury model of acute hyperalgesia.	2001 Jan	11166467
Preoperative rectal diclofenac versus paracetamol for tonsillectomy: effects on pain and blood loss.	2001 Jan	11152033
Effects of diclofenac or ketorolac on the inhibitory activity of cidofovir in the Ad5/NZW rabbit model.	2001 Jan	11133861
Interaction of delavirdine with human liver microsomal cytochrome P450: inhibition of CYP2C9, CYP2C19, and CYP2D6.	2001 Jan	11124228
Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s.	2001 Jan	11124226
Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.	2001 Jan 10	11231885
Bone-specific delivery and sustained release of diclofenac, a non-steroidal anti-inflammatory drug, via bisphosphonic prodrug based on the Osteotropic Drug Delivery System (ODDS).	2001 Jan 29	11166418
[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
Physical incompatibility between atracurium and intravenous diclofenac.	2001 Mar	11251469
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
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

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 `Sat Jun 26 14:26:58 UTC 2021` Edited by `admin` on `Sat Jun 26 14:26:58 UTC 2021`
Record UNII	144O8QL0L1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DICLOFENAC

Official Name

English

DICLOFENAC [MI]

Common Name

English

DICLOFENAC [VANDF]

Common Name

English

DICLOFENAC FREE ACID

Common Name

English

ACECLOFENAC IMPURITY A [EP]

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)-

Common Name

English

DICLOFENAC [USAN]

Common Name

English

DICLOFENAC [WHO-DD]

Common Name

English

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

Common Name

English

Classification Tree Code System Code

WHO-ATC

M01AB05