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
Immune hemolytic anemia associated with tolmetin and suprofen.	1989 Sep	2773031
Multisystem failure and hepatic microvesicular fatty metamorphosis associated with tolmetin ingestion.	1991 Aug	1863194
A population model for tolmetin pharmacokinetics in rats considering saturable elimination.	2001	11793960
Development of an in vitro screening model for the biosynthesis of acyl glucuronide metabolites and the assessment of their reactivity toward human serum albumin.	2002 Apr	11901094
Hepatic covalent adduct formation with zomepirac in the CD26-deficient mouse.	2002 Jan	11895555
Effect of experimental hypoalbuminemia on the plasma protein binding of tolmetin.	2002 Jul 19	12088761
Gastroprotective effects of amtolmetin guacyl: a new non-steroidal anti-inflammatory drug that activates inducible gastric nitric oxide synthase.	2002 Jun	12132787
Investigating the TNP-OVA and direct popliteal lymph node assays for the detection of immunostimulation by drugs associated with anaphylaxis in humans.	2002 May-Jun	12015798
Quantitation of tolmetin by high-performance liquid chromatography and method validation.	2003 Aug	12908956
Detection and disposition of tolmetin in the horse.	2003 Mar 26	12644199
Identification of coenzyme A-related tolmetin metabolites in rats: relationship with reactive drug metabolites.	2003 May	12746110
Alkenyl C-H insertion of iodonium ylides into pyrroles: studies toward the total syntheses of tolmetin and amtolmetin guacil.	2003 May 1	12713311
Identification of zomepirac-S-acyl-glutathione in vitro in incubations with rat hepatocytes and in vivo in rat bile.	2003 Nov	14570776
Spectroscopic behavior of copper complexes of nonsteroidal anti-inflammatory drugs.	2004 May-Jun 5	15137108
Skeletal developmental effects of selective and nonselective cyclooxygenase-2 inhibitors administered through organogenesis and fetogenesis in Wistar CRL:(WI)WUBR rats.	2005 Dec 15	16182428
Kinetic studies on the intramolecular acyl migration of beta-1-O-acyl glucuronides: application to the glucuronides of (R)- and (S)-ketoprofen, (R)- and (S)-hydroxy-ketoprofen metabolites, and tolmetin by 1H-NMR spectroscopy.	2005 Jul	16316930
A competitive low-affinity binding model for determining the mutual and specific sites of two ligands on protein.	2005 Jul 15	15967285
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Multi-residue determination of anti-inflammatory analgesics in sera by liquid chromatography--mass spectrometry.	2005 Mar	15902977
In vitro and in vivo studies on acyl-coenzyme A-dependent bioactivation of zomepirac in rats.	2005 Nov	16300382
Anti-inflammatory and immunosuppressive drugs and reproduction.	2006	16712713
Evidence for the bioactivation of zomepirac and tolmetin by an oxidative pathway: identification of glutathione adducts in vitro in human liver microsomes and in vivo in rats.	2006 Jan	16251255
An exploratory theoretical elucidation on the peroxyl-radical-scavenging mechanism and structure-activity relationship of nonsteroidal anti-inflammatory drugs.	2006 Jun 15	16600595
Scavenging of reactive oxygen species by some nonsteroidal anti-inflammatory drugs and fenofibrate.	2006 Jun 5	16245331
Celosomy is associated with prenatal exposure to cyclooxygenase inhibitors.	2006 Mar	16460959
Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels.	2006 Nov 10	16952380
Non-steroidal anti-inflammatory agents, tolmetin and sulindac, attenuate oxidative stress in rat brain homogenate and reduce quinolinic acid-induced neurodegeneration in rat hippocampal neurons.	2006 Sep	16850258
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 Aug 3	17300791
Potential antioxidant activity of celecoxib and amtolmetin guacyl: in vitro studies.	2007 Jan	17199871
Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin.	2007 Jan 31	17243824
A simple in vitro model to study the stability of acylglucuronides.	2007 Jan-Feb	16713308
Determination of degradation pathways and kinetics of acyl glucuronides by NMR spectroscopy.	2007 Jun	17536843
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 Mar 20	17266991
Improving adherence to medical regimens for juvenile rheumatoid arthritis.	2007 May 18	17550635
Modulation of dopaminergic neurotransmission in rat striatum upon in vitro and in vivo diclofenac treatment.	2008 Apr	18036194
Ionic liquid-based dynamic liquid-phase microextraction: application to the determination of anti-inflammatory drugs in urine samples.	2008 Aug 15	18632109
Topical ocular delivery of NSAIDs.	2008 Jun	18437583
Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan.	2009	18815725
Glycerolysis of acyl glucuronides as an artifact of in vitro drug metabolism incubations.	2009 Aug	19439485
Drug-organic electrolyte complexes as controlled release systems.	2009 Jan	18991061
A study of the intermolecular interactions of tolmetin/N-acetyl-L-tyrosine ethyl ester complex.	2009 Jun	19181568
Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development.	2009 Sep	19379806
Accuracy of rapid urease test in diagnosing Helicobacter pylori infection in patients using NSAIDs.	2010 Apr-Jun	20339181
Friedel-Crafts acylation of pyrroles and indoles using 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) as a nucleophilic catalyst.	2010 Dec 17	21077631
Nonsteroidal Anti-Inflammatory Drugs: A survey of practices and concerns of pediatric medical and surgical specialists and a summary of available safety data.	2010 Feb 4	20181090
Unusual interleukin-1 and -6 expression in fetal cartilage is associated with placental abnormalities.	2010 Jan 1	20529813
Control of encapsulation efficiency in polymeric microparticle system of tolmetin.	2010 Jan-Feb	19505209
Diclofenac hypersensitivity: antibody responses to the parent drug and relevant metabolites.	2010 Oct 28	21060839
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 Jan	24085192
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541

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