TOLMETIN SODIUM ANHYDROUS

First approved in 1976

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H14NO3.Na
Molecular Weight	279.2663
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CN1C(CC([O-])=O)=CC=C1C(=O)C2=CC=C(C)C=C2

InChI

InChIKey=QGUALMNFRILWRA-UHFFFAOYSA-M

InChI=1S/C15H15NO3.Na/c1-10-3-5-11(6-4-10)15(19)13-8-7-12(16(13)2)9-14(17)18;/h3-8H,9H2,1-2H3,(H,17,18);/q;+1/p-1

HIDE SMILES / InChI

Molecular Formula	Na
Molecular Weight	22.98976928
Charge	1
Count

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

Molecular Formula	C15H14NO3
Molecular Weight	256.2766
Charge	-1
Count

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018084s052,017628s068lbl.pdf | https://www.drugbank.ca/drugs/DB00500

Tolmetin is a nonsteroidal anti-inflammatory agent. It was marketed as Tolectin in USA. TOLECTIN (tolmetin sodium) is indicated for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis. TOLECTIN is indicated in the treatment of acute flares and the long-term management of the chronic disease. TOLECTIN is also indicated for treatment of juvenile rheumatoid arthritis. The mode of action of tolmetin is not known. However, studies in laboratory animals and man have demonstrated that the anti-inflammatory action of tolmetin is not due to pituitary-adrenal stimulation. Tolmetin inhibits prostaglandin synthetase in vitro and lowers the plasma level of prostaglandin E in man. This reduction in prostaglandin synthesis may be responsible for the anti-inflammatory action.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase-1 131 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10465690 \| http://www.genome.jp/dbget-bin/www_bget?D02355	Inhibitor 8504	0.35 µM [IC50]
Cyclooxygenase-2 201 Target ID: CHEMBL230 Sources: http://www.genome.jp/dbget-bin/www_bget?D02355 \| https://www.drugbank.ca/drugs/DB00500	Inhibitor 8504	0.82 µM [IC50]
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16396699\|https://adisinsight.springer.com/drugs/800002179	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 320 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018084s052,017628s068lbl.pdf	Primary		Approved 8583	Tolmetin sodium Approved Use Carefully consider the potential benefits and risks of tolmetin sodium capsules and other treatment options before deciding to use tolmetin sodium capsules. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS). Tolmetin sodium capsules are indicated for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis. Tolmetin sodium capsules are indicated in the treatment of acute flares and the long-term management of the chronic disease. Tolmetin sodium capsules are also indicated for treatment of juvenile rheumatoid arthritis. The safety and effectiveness of tolmetin sodium capsules have not been established in pediatric patients under 2 years of age. Launch Date 1976
Osteoarthritis 157 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018084s052,017628s068lbl.pdf	Primary		Approved 8583	Tolmetin sodium Approved Use Carefully consider the potential benefits and risks of tolmetin sodium capsules and other treatment options before deciding to use tolmetin sodium capsules. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS). Tolmetin sodium capsules are indicated for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis. Tolmetin sodium capsules are indicated in the treatment of acute flares and the long-term management of the chronic disease. Tolmetin sodium capsules are also indicated for treatment of juvenile rheumatoid arthritis. The safety and effectiveness of tolmetin sodium capsules have not been established in pediatric patients under 2 years of age. Launch Date 1976

C_max

Value	Dose	Co-administered	Analyte	Population
29.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1126116/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		TOLMETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
50.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1126116/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		TOLMETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.83 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1126116/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		TOLMETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
400 mg 3 times / day steady, oral Dose: 400 mg, 3 times / day Route: oral Route: steady Dose: 400 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018084s052,017628s068lbl.pdf	unhealthy, adults Health Status: unhealthy Age Group: adults Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018084s052,017628s068lbl.pdf	Other AEs: Nausea, Dyspepsia... Other AEs: Nausea (11%) Dyspepsia (3-9) Distress gastrointestinal (3-9) Abdominal pain (3-9) Diarrhea (3-9) Flatulence (3-9) Vomiting (3-9) Constipation (1-3) Gastritis (1-3) Peptic ulcer (1-3) Headache (3-9) Asthenia (3-9) Chest pain (1-3) Blood pressure increased (3-9) Edema (3-9) Dizziness (3-9) Drowsiness (3-9) Depression (1-3) Weight gain (3-9) Weight loss (3-9) Skin irritation (1-3) Tinnitus (1-3) Visual disturbance (1-3) Blood urea nitrogen increased (1-3) Urinary tract infection (1-3) Gastrointestinal ulcer bleeding (<1%) Bleeding gastrointestinal (<1%) Perforation (<1%) Glossitis (<1%) Stomatitis (<1%) Hepatitis (<1%) Function liver abnormal (<1%) Anaphylactoid reaction (<1%) Fever (<1%) Lymphadenopathy (<1%) Serum sickness (<1%) Hemolytic anemia (<1%) Thrombocytopenia (<1%) Granulocytopenia (<1%) Agranulocytosis (<1%) Urticaria (<1%) Purpura (<1%) Erythema multiforme (<1%) Toxic epidermal necrolysis (<1%) Hematuria (<1%) Proteinuria (<1%) Dysuria (<1%) Renal failure (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018084s052,017628s068lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP2 499 MRP4 290	UGT 219

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
MRP4 345	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17005917/	yes [IC50 20.5 uM]
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17005917/	yes [IC50 494 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16251255/	yes
UGT 219	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31839590/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:71941	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:71941
ChemicalBook	CB2875183	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2875183
ChemicalBook	CB84634335	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB84634335
eMolecules	5753460	https://www.emolecules.com/cgi-bin/more?vid=5753460
ZINC	ZINC000000002191	http://zinc15.docking.org/substances/ZINC000000002191

PubMed

Title	Date	PubMed
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015-05-18	25811541
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.	2014-01	24085192
Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.	2012-12	22733274
Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients.	2010-12-31	21194458
Friedel-Crafts acylation of pyrroles and indoles using 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) as a nucleophilic catalyst.	2010-12-17	21077631
Determination of actarit from human plasma for bioequivalence studies.	2010-11	21969744
Diclofenac hypersensitivity: antibody responses to the parent drug and relevant metabolites.	2010-10-28	21060839
Validation and clinical application of an LC-ESI-MS/MS method for simultaneous determination of tolmetin and MED5, the metabolites of amtolmetin guacil in human plasma.	2010-10	20853464
Effect of ketorolac and diclofenac on the impairment of endothelium-dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta.	2010-09	20877705
An evaluation of the utility of routine laboratory monitoring of juvenile idiopathic arthritis (JIA) patients using non-steroidal anti-inflammatory drugs (NSAIDs): a retrospective review.	2010-04-14	20398286
Accuracy of rapid urease test in diagnosing Helicobacter pylori infection in patients using NSAIDs.	2010-03-27	20339181
Nonsteroidal Anti-Inflammatory Drugs: A survey of practices and concerns of pediatric medical and surgical specialists and a summary of available safety data.	2010-02-04	20181090
Unusual interleukin-1 and -6 expression in fetal cartilage is associated with placental abnormalities.	2010-01-01	20529813
Development of theophylline floating microballoons using cellulose acetate butyrate and/or Eudragit RL 100 polymers with different permeability characteristics.	2010-01	21589766
Evaluation of Wound Healing Potential of Bauhinia purpurea Leaf Extracts in Rats.	2010-01	20582204
Effect of formulation and processing variables on the characteristics of tolmetin microspheres prepared by double emulsion solvent diffusion method.	2010-01	20582193
Entrapment of ketorolac tromethamine in polymeric vehicle for controlled drug delivery.	2009-11	20376226
Sequential injection system for phospholipase A2 activity evaluation: studies on liposomes using an environment-sensitive fluorescent probe.	2009-09-15	19615520
Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development.	2009-09	19379806
Glycerolysis of acyl glucuronides as an artifact of in vitro drug metabolism incubations.	2009-08	19439485
Control of encapsulation efficiency in polymeric microparticle system of tolmetin.	2009-06-10	19505209
A study of the intermolecular interactions of tolmetin/N-acetyl-L-tyrosine ethyl ester complex.	2009-06	19181568
Drug-organic electrolyte complexes as controlled release systems.	2009-01	18991061
Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan.	2009	18815725
The effect of piroxicam on the formation of postoperative, intraabdominal adhesion in rats.	2008-10	19568538
A novel high-throughput screening assay for putative antidiabetic agents through PPARalpha interactions.	2008-10	18812576
Ionic liquid-based dynamic liquid-phase microextraction: application to the determination of anti-inflammatory drugs in urine samples.	2008-08-15	18632109
Topical ocular delivery of NSAIDs.	2008-06	18437583
Modulation of dopaminergic neurotransmission in rat striatum upon in vitro and in vivo diclofenac treatment.	2008-04	18036194
Singlet oxygen scavenging activity of non-steroidal anti-inflammatory drugs.	2008	18647485
Role of biotransformation studies in minimizing metabolism-related liabilities in drug discovery.	2008	18446518
Cyclooxygenase inhibitors affect bone mineralization in rat fetuses.	2008	17992008
Idiopathic chondrolysis of the hip: a case report.	2007-10	18019924
Determination of non-steroidal anti-inflammatory drugs in urine by combining an immobilized carboxylated carbon nanotubes minicolumn for solid-phase extraction with capillary electrophoresis-mass spectrometry.	2007-08-03	17300791
A peripatetic pediatrician's journey into pediatric rheumatology: Part II.	2007-06-21	17584931
Determination of degradation pathways and kinetics of acyl glucuronides by NMR spectroscopy.	2007-06	17536843
Improving adherence to medical regimens for juvenile rheumatoid arthritis.	2007-05-18	17550635
Studies on the metabolism of tolmetin to the chemically reactive acyl-coenzyme A thioester intermediate in rats.	2007-05	17303625
In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems. Comparison with non-selective and COX-2 selective NSAIDs.	2007-04	17391279
One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.	2007-04	17381629
Non-steroidal anti-inflammatory agents, tolmetin and sulindac attenuate quinolinic acid (QA)-induced oxidative stress in primary hippocampal neurons and reduce QA-induced spatial reference memory deficits in male Wistar rats.	2007-03-20	17266991
Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin.	2007-01-31	17243824
In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems in different models of gastrointestinal injury.	2007-01	17199877
Potential antioxidant activity of celecoxib and amtolmetin guacyl: in vitro studies.	2007-01	17199871
Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport.	2007-01	17005917
Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels.	2006-11-10	16952380
I almost crossed over.	2005-10	17094512
Naproxen-induced recurrent aseptic meningitis.	1991-11	1763533
Multisystem failure and hepatic microvesicular fatty metamorphosis associated with tolmetin ingestion.	1991-08	1863194
Immune hemolytic anemia associated with tolmetin and suprofen.	1989-09	2773031

Patents

Sample Use Guides

In Vivo Use Guide

For the relief of rheumatoid arthritis or osteoarthritis, the recommended starting dose for adults is 400 mg three times daily (1200 mg daily), preferably including a dose on arising and a dose at bedtime. To achieve optimal therapeutic effect the dose should be adjusted according to the patient’s response after one or two weeks. Control is 15 usually achieved at doses of 600-1800 mg daily in divided doses (generally t.i.d.). Doses larger than 1800 mg/day have not been studied and are not recommended.

Route of Administration: Oral

In Vitro Use Guide

Tolmetin inhibited the activity of human COX-1 and -2 with IC50 values of 0.35 and 0.82 uM, respectively

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:13:04 GMT 2025` Edited by `admin` on `Mon Mar 31 18:13:04 GMT 2025`
Record UNII	WL259637KX
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TOLMETIN SODIUM ANHYDROUS

Common Name

English

1H-PYRROLE-2-ACETIC ACID, 1-METHYL-5-(4-METHYLBENZOYL)-, SODIUM SALT

Preferred Name

English

1H-PYRROLE-2-ACETIC ACID, 1-METHYL-5-(4-METHYLBENZOYL)-, SODIUM SALT (1:1)

Common Name

English

Tolmetin sodium [WHO-DD]

Common Name

English

SODIUM TOLMETIN

Common Name

English

SODIUM 1-METHYL-5-P-TOLUOYLPYRROLE-2-ACETATE

Common Name

English

Code System Code Type Description

CHEBI

9619