TOLMETIN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H15NO3
Molecular Weight	257.2845
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CN1C(CC(O)=O)=CC=C1C(=O)C2=CC=C(C)C=C2

InChI

InChIKey=UPSPUYADGBWSHF-UHFFFAOYSA-N

InChI=1S/C15H15NO3/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)

HIDE SMILES / InChI

Molecular Formula	C15H15NO3
Molecular Weight	257.2845
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

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-1 127	Inhibitor 8,297	0.35 µM [IC50]
Cyclooxygenase-2 196	Inhibitor 8,297	0.82 µM [IC50]
Cyclooxygenase 89	Inhibitor 8,297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 316	Primary		Approved 8,429	Tolmetin sodium
Osteoarthritis 157	Primary		Approved 8,429	Tolmetin sodium

C_max

Value	Dose	Co-administered	Analyte	Population
29.3 μg/mL	300 mg single, oral		TOLMETIN plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
50.5 μg × h/mL	300 mg single, oral		TOLMETIN plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.83 h	300 mg single, oral		TOLMETIN plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
400 mg 3 times / day steady, oral (starting)	unhealthy, adults n = 800	Other AEs: Nausea, Dyspepsia...

Showing 1 to 1 of 1 entries

Previous1Next

AEs

Show entries

AE	Significance	Dose	Population
Blood urea nitrogen increased	1-3	400 mg 3 times / day steady, oral (starting)	unhealthy, adults n = 800
Chest pain	1-3	400 mg 3 times / day steady, oral (starting)	unhealthy, adults n = 800
Constipation	1-3	400 mg 3 times / day steady, oral (starting)	unhealthy, adults n = 800
Depression	1-3	400 mg 3 times / day steady, oral (starting)	unhealthy, adults n = 800
Gastritis	1-3	400 mg 3 times / day steady, oral (starting)	unhealthy, adults n = 800

Showing 1 to 5 of 48 entries

Previous1 2 3 4 5…10Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP2 383 MRP4 204	UGT 192

Drug as perpetrator

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
MRP4 238	inhibitor 3,277	yes [IC50 20.5 uM]
MRP2 475	inhibitor 3,277	yes [IC50 494 uM]

Showing 1 to 2 of 2 entries

Previous1Next

Drug as victim

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1,737	substrate 3,367	yes
UGT 192	substrate 3,367	yes

Showing 1 to 2 of 2 entries

Previous1Next

Sourcing

Sourcing

Show entries

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
ZINC	ZINC000000002191	http://zinc15.docking.org/substances/ZINC000000002191
eMolecules	5753460	https://www.emolecules.com/cgi-bin/more?vid=5753460

Showing 1 to 5 of 5 entries

Previous1Next

PubMed

Show entries

Title	Date	PubMed
Naproxen-induced recurrent aseptic meningitis.	1991 Nov	1763533
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Hepatic covalent adduct formation with zomepirac in the CD26-deficient mouse.	2002 Jan	11895555
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

Showing 1 to 5 of 19 entries

Previous1 2 3 4Next

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