Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H16ClNO4 |
Molecular Weight | 357.788 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC2=C(C=C1)N(C(=O)C3=CC=C(Cl)C=C3)C(C)=C2CC(O)=O
InChI
InChIKey=CGIGDMFJXJATDK-UHFFFAOYSA-N
InChI=1S/C19H16ClNO4/c1-11-15(10-18(22)23)16-9-14(25-2)7-8-17(16)21(11)19(24)12-3-5-13(20)6-4-12/h3-9H,10H2,1-2H3,(H,22,23)
DescriptionCurator's Comment: description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT02183168 | https://clinicaltrials.gov/ct2/show/NCT02770950 | https://www.ncbi.nlm.nih.gov/pubmed/20503989 | https://www.ncbi.nlm.nih.gov/pubmed/14056924 | https://www.ncbi.nlm.nih.gov/pubmed/27988363
Curator's Comment: description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT02183168 | https://clinicaltrials.gov/ct2/show/NCT02770950 | https://www.ncbi.nlm.nih.gov/pubmed/20503989 | https://www.ncbi.nlm.nih.gov/pubmed/14056924 | https://www.ncbi.nlm.nih.gov/pubmed/27988363
Indometacin (INN and BAN) or indomethacin (AAN, USAN, and former BAN) is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. Indomethacin has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of Indometacin, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2). Indomethacin is a potent inhibitor of prostaglandin synthesis in vitro. Indomethacin concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because indomethacin is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues. Indometacin is indicated for: Moderate to severe rheumatoid arthritis including acute flares of chronic disease, Moderate to severe ankylosing spondylitis, Moderate to severe osteoarthritis, Acute painful shoulder (bursitis and/or tendinitis), Acute gouty arthritis. In general, adverse effects seen with indomethacin are similar to all other NSAIDs. For instance, indometacin inhibits both cyclooxygenase-1 and cyclooxygenase-2, it inhibits the production of prostaglandins in the stomach and intestines, which maintain the mucous lining of the gastrointestinal tract. Indometacin, therefore, like other non-selective COX inhibitors can cause peptic ulcers. These ulcers can result in serious bleeding and/or perforation requiring hospitalization of the patient. To reduce the possibility of peptic ulcers, indomethacin should be prescribed at the lowest dosage needed to achieve a therapeutic effect, usually between 50–200 mg/day. It should always be taken with food. Nearly all patients benefit from an ulcer protective drug (e.g. highly dosed antacids, ranitidine 150 mg at bedtime, or omeprazole 20 mg at bedtime). Other common gastrointestinal complaints, including dyspepsia, heartburn and mild diarrhea are less serious and rarely require discontinuation of indomethacin.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11906281 |
3.0 nM [IC50] | ||
Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20503989 |
10.0 nM [IC50] | ||
Target ID: CHEMBL4681 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23432095 |
100.0 nM [IC50] | ||
Target ID: CHEMBL1835 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2547071 |
100.0 nM [IC50] | ||
Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12142058 |
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Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12142058 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | INDOCIN Approved UseTIVORBEX is indicated for treatment of mild to moderate acute pain in adults. TIVORBEX is a NSAID indicated for treatment of mild to moderate acute pain in adults (1). Launch Date1965 |
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Primary | INDOCIN Approved UseTIVORBEX is indicated for treatment of mild to moderate acute pain in adults. TIVORBEX is a NSAID indicated for treatment of mild to moderate acute pain in adults (1). Launch Date1965 |
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Primary | INDOCIN Approved UseTIVORBEX is indicated for treatment of mild to moderate acute pain in adults. TIVORBEX is a NSAID indicated for treatment of mild to moderate acute pain in adults (1). Launch Date1965 |
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Primary | INDOCIN Approved UseTIVORBEX is indicated for treatment of mild to moderate acute pain in adults. TIVORBEX is a NSAID indicated for treatment of mild to moderate acute pain in adults (1). Launch Date1965 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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2 μg/mL |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
INDOMETHACIN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
2369 ng/mL |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
INDOMETHACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7762 ng × h/mL |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
INDOMETHACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.22 h |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
INDOMETHACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
INDOMETHACIN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
PubMed
Title | Date | PubMed |
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Letter: Aspirin sensitivity: other drugs. | 1975 Feb |
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[Evaluation of the effects of some non-steroid anti-inflammatory agents on the gastric mucosa]. | 1976 Jul 7 |
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[Intrahepatic cholestasis following treatment with penicillamine D and indomethacine]. | 1976 May 28 |
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Premature onset of labor, neonatal patent ductus arteriosus, and prostaglandin synthetase antagonists--a rat model of a human problem. | 1979 Sep 15 |
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Decrease in nucleophosmin/B23 mRNA and telomerase activity during indomethacin-induced apoptosis of gastric KATO-III cancer cells. | 1999 Dec |
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Prostaglandin-independent anovulatory mechanism of indomethacin action: inhibition of tumor necrosis factor alpha-induced sheep ovarian cell apoptosis. | 1999 Dec |
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The effect of indomethacin on the cytokine cascade and body temperature following burn injury in rats. | 1999 Jun |
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Indomethacin reduces the skin thermal damage in hyperthermic treatment of experimental malignant tumors. | 1999 May-Jun |
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Capsaicin-sensitive afferent sensory nerves in modulating gastric mucosal defense against noxious agents. | 1999 Nov |
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Effect of anti-CD11b (alphaM-MAC-1) and anti-CD54 (ICAM-1) monoclonal antibodies on indomethacin induced chronic ileitis in rats. | 1999 Nov |
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Indomethacin treatment decreases renal blood flow velocity in human neonates. | 1999 Nov |
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Role of prostaglandins generated by cyclooxygenase-1 and cyclooxygenase-2 in healing of ischemia-reperfusion-induced gastric lesions. | 1999 Nov 26 |
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Indomethacin induced gastropathy in CD18, intercellular adhesion molecule 1, or P-selectin deficient mice. | 1999 Oct |
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Indomethacin-induced postoperative psychosis. | 1999 Sep |
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Persistent pulmonary hypertension after maternal naproxen ingestion in a term newborn: a case report. | 2000 |
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[Effect of carrageenan and indomethacin on the growth of a murine fibrosarcoma]. | 2000 |
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Indomethacin inhibits endothelial cell proliferation by suppressing cell cycle proteins and PRB phosphorylation: a key to its antiangiogenic action? | 2000 Aug |
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Non-steroidal anti-inflammatory drugs with different cyclooxygenase inhibitory profiles that prevent aberrant crypt foci formation but vary in acute gastrotoxicity in a rat model. | 2000 Dec |
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Neuropeptide Y enhances potassium excretion by mechanisms distinct from those controlling sodium excretion. | 2000 Feb |
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Randomized double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus. | 2000 Jan |
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Inhibition of carrageenan-induced edema by indomethacin or sodium salicylate does not prevent the increase of nerve growth factor in the rat hind paw. | 2000 Jan 14 |
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Prevention and healing of experimental indomethacin-induced gastric lesions: effects of ebrotidine, omeprazole and ranitidine. | 2000 Mar |
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Effects of hydrogen peroxide scavenger Catalase on villous microcirculation in the rat small intestine in a model of inflammatory bowel disease. | 2000 May |
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Role of endothelin-converting enzyme-1 in the suppression of constitutive nitric oxide synthase in rat gastric mucosal injury by indomethacin. | 2000 Nov |
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Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril. | 2000 Nov |
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Inhibition of proteolysis by a cyclooxygenase inhibitor, indomethacin. | 2000 Nov |
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Keratinocyte growth factor-2 (FGF-10) promotes healing of experimental small intestinal ulceration in rats. | 2000 Nov |
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Inhibition of inducible nitric oxide synthase gene expression by indomethacin or ibuprofen in beta-amyloid protein-stimulated J774 cells. | 2000 Nov 17 |
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A case of living-related kidney transplantation in Bartter's syndrome. | 2000 Oct |
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Protection by polaprezinc, an anti-ulcer drug, against indomethacin-induced apoptosis in rat gastric mucosal cells. | 2000 Sep |
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Suppressed injury-induced rise in spinal prostaglandin E2 production and reduced early thermal hyperalgesia in iNOS-deficient mice. | 2000 Sep 1 |
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Effect of the nonsteroidal anti-inflammatory drug indomethacin on proliferation and apoptosis of colon carcinoma cells. | 2001 |
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Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations. | 2001 |
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Stimulation of cyclooxygenase-2-activity by nitric oxide-derived species in rat chondrocyte: lack of contribution to loss of cartilage anabolism. | 2001 Apr 15 |
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Indomethacin increases 15-PGDH mRNA expression in HL60 cells differentiated by PMA. | 2001 Feb |
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Does exposure to magnesium sulfate in utero decrease the risk of necrotizing enterocolitis in premature infants? | 2001 Feb |
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Upregulation of angiotensin-converting enzyme by vascular endothelial growth factor. | 2001 Feb |
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Lack of small intestinal ulcerogenecity of nitric oxide-releasing indomethacin, NCX-530, in rats. | 2001 Feb |
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Increased 15-HPETE production decreases prostacyclin synthase activity during oxidant stress in aortic endothelial cells. | 2001 Feb 1 |
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An investigation into the thermal behaviour of an amorphous drug using low frequency dielectric spectroscopy and modulated temperature differential scanning calorimetry. | 2001 Jan |
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Effect of Lactobacillus ingestion on the gastrointestinal mucosal barrier alterations induced by indometacin in humans. | 2001 Jan |
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Review article: the gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase-2, in humans. | 2001 Jan |
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Protective role of cyclooxygenase inhibitors in the adverse action of passive cigarette smoking on the initiation of experimental colitis in rats. | 2001 Jan 5 |
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Agonist-specific regulation of monocyte chemoattractant protein-1 expression by cyclooxygenase metabolites in hepatic stellate cells. | 2001 Mar |
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Effect of indomethacin on gallbladder inflammation and contractility during acute cholecystitis. | 2001 Mar |
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Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. | 2001 Mar |
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Comparative effects of indomethacin on cell proliferation and cell cycle progression in tumor cells grown in vitro and in vivo. | 2001 Mar 1 |
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Inactivation of creatine kinase during the interaction of indomethacin with horseradish peroxidase and hydrogen peroxide: involvement of indomethacin radicals. | 2001 Mar 14 |
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Indomethacin prevents the induction of inducible nitric oxide synthase in murine peritoneal macrophages and decreases their nitric oxide production. | 2001 Mar 9 |
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Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice. | 2001 Mar 9 |
Patents
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27988363
U251 cells were incubated for 24 h with different concentrations of indomethacin (0.03, 0.06, 0.13, 0.25, 0.5, 1 mkM), diclofenac (DIC),naproxen (NAP), or ketoprofen (KET), and the cell viability was assessed by MTT or crystal violet (CV) tests.
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000000160
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NCI_THESAURUS |
C1323
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WHO-VATC |
QS01BC01
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WHO-VATC |
QC01EB03
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NCI_THESAURUS |
C54677
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NDF-RT |
N0000175721
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LIVERTOX |
NBK548001
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WHO-ATC |
M02AA23
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NDF-RT |
N0000175722
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WHO-VATC |
QM01AB01
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WHO-ATC |
M01AB01
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WHO-ATC |
S01BC01
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WHO-VATC |
QM02AA23
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WHO-ATC |
S01CC02
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WHO-VATC |
QM01AB51
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WHO-ATC |
M01AB51
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WHO-ATC |
C01EB03
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CHEMBL6
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DB00328
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m6279
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PRIMARY | Merck Index | ||
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5781
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PRIMARY | RxNorm | ||
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D007213
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Indomethacin
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XXE1CET956
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DTXSID9020740
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SUB08180MIG
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100000092758
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49662
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757061
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1524
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77541
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1341001
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3101
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3715
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INDOMETHACIN
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PRIMARY | Description: A white or a pale yellow, crystalline powder; odourless or almost odourless. Solubility: Practically insoluble in water; sparingly soluble in ethanol (~750 g/l) TS and ether R. Category: Analgesic; anti-inflammatory. Storage: Indometacin should be kept in a well-closed container, protected from light. Additional information: Indometacin exhibits polymorphism. The polymorph specified in the monograph corresponds to the crystal form of indometacin RS.Definition: Indometacin contains not less than 98.0% and not more than 101.0% of C19H16ClNO4, calculated with reference to the dried substance. | ||
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1440
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C576
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53-86-1
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1909
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200-186-5
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INDOMETACIN
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
PRODRUG (METABOLITE ACTIVE)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)