Details
Stereochemistry | ACHIRAL |
Molecular Formula | C14H11Cl2NO2.C4H11N |
Molecular Weight | 369.285 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCNCC.OC(=O)CC1=C(NC2=C(Cl)C=CC=C2Cl)C=CC=C1
InChI
InChIKey=ZQVZPANTCLRASL-UHFFFAOYSA-N
InChI=1S/C14H11Cl2NO2.C4H11N/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19;1-3-5-4-2/h1-7,17H,8H2,(H,18,19);5H,3-4H2,1-2H3
DescriptionSources: https://www.drugs.com/pro/diclofenac.htmlCurator'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
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.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3085489
Curator's Comment: reference retrieved from http://www.pharmaceutical-journal.com/news-and-analysis/news/diclofenac-a-useful-drug-that-may-now-be-entering-its-twilight-years/11121261.article
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
0.97 nM [IC50] | |||
0.037 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | DICLOFENAC SODIUM Approved UseDiclofenac 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 |
|||
Primary | DICLOFENAC SODIUM Approved UseDiclofenac 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 |
Cmax
Value | Dose | Co-administered | 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 | Co-administered | 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 |
T1/2
Value | Dose | Co-administered | 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 |
unknown, oral |
DICLOFENAC serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
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: |
healthy, 18 - 53 years Health Status: healthy Age Group: 18 - 53 years Sex: M+F Sources: |
|
50 mg single, oral |
healthy, 21-51 years n = 24 Health Status: healthy Age Group: 21-51 years Sex: M+F Population Size: 24 Sources: |
Other AEs: Nephrotoxicity... |
500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: |
unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: |
Disc. AE: Drowsiness, Lethargy... AEs leading to discontinuation/dose reduction: Drowsiness Sources: Lethargy Nausea Vomiting Epigastric pain |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Nephrotoxicity | 50 mg single, oral |
healthy, 21-51 years n = 24 Health Status: healthy Age Group: 21-51 years Sex: M+F Population Size: 24 Sources: |
|
Drowsiness | Disc. AE | 500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: |
unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: |
Epigastric pain | Disc. AE | 500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: |
unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: |
Lethargy | Disc. AE | 500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: |
unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: |
Nausea | Disc. AE | 500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: |
unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: |
Vomiting | Disc. AE | 500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: |
unknown, adult Health Status: unknown Age Group: adult Sex: unknown Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
moderate | ||||
no | ||||
no | ||||
no | ||||
no | ||||
strong | ||||
weak | ||||
weak | ||||
weak | ||||
yes [Ki 11 uM] | ||||
yes [Ki 19 uM] | ||||
yes [Ki 28 uM] | ||||
yes [Ki 52 uM] | ||||
yes [Ki 60 uM] | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
minor | ||||
minor | ||||
minor | ||||
moderate | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Multiple diclofenac-induced adverse effects. | 2000 Oct |
|
Cytochrome P-450 2C9 sensitizes human prostate tumor cells to cyclophosphamide via a bystander effect. | 2000 Oct |
|
Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six weeks treatment in patients with osteoarthritis. | 2001 |
|
Celecoxib versus diclofenac in the management of osteoarthritis of the knee. | 2001 |
|
Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations. | 2001 |
|
Cataflam-induced esophageal ulceration. | 2001 Apr |
|
Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs. | 2001 Apr |
|
The role of matrix metalloproteinases in ulcerative keratolysis associated with perioperative diclofenac use. | 2001 Apr |
|
Tramadol vs. diclofenac for posttonsillectomy analgesia. | 2001 Apr |
|
Treatment of elderly patients with nabumetone or diclofenac: gastrointestinal safety profile. | 2001 Apr |
|
The epithelial flap for photorefractive keratectomy. | 2001 Apr |
|
Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors. | 2001 Apr |
|
Equivalence of generic and brand-name ophthalmic products. | 2001 Apr 1 |
|
Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system. | 2001 Apr 28 |
|
Determination of diclofenac sodium, flufenamic acid, indomethacin and ketoprofen by LC-APCI-MS. | 2001 Feb |
|
When should diclofenac be given in ambulatory surgery: preoperatively or postoperatively? | 2001 Feb |
|
Minocycline inhibits the production of inducible nitric oxide synthase in articular chondrocytes. | 2001 Feb |
|
Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo. | 2001 Feb |
|
Endothelial dysfunction and salt-sensitive hypertension in spontaneously diabetic Goto-Kakizaki rats. | 2001 Feb |
|
Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia. | 2001 Feb |
|
Effects of anti-inflammatory drugs following cataract extraction. | 2001 Feb |
|
Simulation of skin permeability in chitosan membranes. | 2001 Feb 1 |
|
Mechanisms of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery. | 2001 Feb 2 |
|
Determination of drug residues in water by the combination of liquid chromatography or capillary electrophoresis with electrospray mass spectrometry. | 2001 Feb 23 |
|
Truth and consequences. | 2001 Jan |
|
Truth and consequences. | 2001 Jan |
|
Renal colic and recurrent urinary calculi. Management and prevention. | 2001 Jan |
|
Truth and consequences. | 2001 Jan |
|
Misoprostol therapeutics revisited. | 2001 Jan |
|
Inhibition of the nitrosothiol production of cultured osteoarthritic chondrocytes by rhein, cortisol and diclofenac. | 2001 Jan |
|
High-dose intrathecal diamorphine for analgesia after Caesarean section. | 2001 Jan |
|
Effects of diclofenac in the rat tail ischaemia--reperfusion injury model of acute hyperalgesia. | 2001 Jan |
|
Interaction of delavirdine with human liver microsomal cytochrome P450: inhibition of CYP2C9, CYP2C19, and CYP2D6. | 2001 Jan |
|
A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s using an in vitro cocktail of probe substrates and fast gradient liquid chromatography tandem mass spectrometry. | 2001 Jan |
|
Sublingual morphine may be a suitable alternative for pain control in children in the postoperative period. | 2001 Jan |
|
Hyperkalaemic quadriparesis secondary to chronic diclofenac treatment. | 2001 Jan |
|
Behavioral suppression induced by cannabinoids is due to activation of the arachidonic acid cascade in rats. | 2001 Jan 19 |
|
Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin. | 2001 Jan 5 |
|
Analgesic effect of epidural neostigmine after abdominal hysterectomy. | 2001 Mar |
|
An assessment of the clinical efficacy of intranasal desmopressin spray in the treatment of renal colic. | 2001 Mar |
|
Role of the epithelium in opposing H(2)O(2)-induced modulation of acetylcholine-induced contractions in rabbit intrapulmonary bronchiole. | 2001 Mar |
|
Cytochrome P450 expression and related metabolism in human buccal mucosa. | 2001 Mar |
|
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 |
|
Metabolic characterization of the major human small intestinal cytochrome p450s. | 2001 Mar |
|
Simultaneous quantification of neutral and acidic pharmaceuticals and pesticides at the low-ng/l level in surface and waste water. | 2001 Mar 16 |
|
Use of ion-exchange resins to prepare 100 microm-sized microcapsules with prolonged drug-release by the Wurster process. | 2001 Mar 23 |
|
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. | 2001 May |
|
Structure-hepatic disposition relationships for cationic drugs in isolated perfused rat livers: transmembrane exchange and cytoplasmic binding process. | 2001 May |
|
Characterization of rat and human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of diclofenac. | 2001 May |
|
Diclofenac sodium injection sterilized by autoclave and the occurrence of cyclic reaction producing a small amount of impurity. | 2001 May |
Patents
Sample Use Guides
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22330146
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).
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C257
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115087
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6TGQ35Z71K
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100000091074
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C87322
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SUB01669MIG
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236125
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DTXSID40999449
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78213-16-8
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Diclofenac diethylamine
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DBSALT001945
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m4361
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PRIMARY | Merck Index |
ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD