Tolmetin
Identification
- Summary
Tolmetin is an NSAID used to treat acute flares of various painful conditions and used for the long term management of osteoarthritis, rheumatoid arthritis, and juvenile arthritis.
- Generic Name
- Tolmetin
- DrugBank Accession Number
- DB00500
- Background
A non-steroidal anti-inflammatory agent (anti-inflammatory agents, NON-steroidal) similar in mode of action to indomethacin.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 257.2845
Monoisotopic: 257.105193351 - Chemical Formula
- C15H15NO3
- Synonyms
- 1-Methyl-5-(4-methylbenzoyl)-pyrrole-2-acetic acid
- 1-Methyl-5-p-toluoylpyrrole-2-acetic acid
- 5-(p-Toluoyl)-1-methylpyrrole-2-acetic acid
- Tolmetin
- Tolmetina
- Tolmétine
- Tolmetino
- Tolmetinum
- External IDs
- McN 2559
- McN 2559-21-98
- MCN-2559
Pharmacology
- Indication
For the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis, including the treatment of acute flares long-term management. Also for treatment of juvenile rheumatoid arthritis.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Ankylosing spondylitis (as) •••••••••••• ••••••• Treatment of Osteoarthritis (oa) •••••••••••• ••••••• Treatment of Rheumatoid arthritis •••••••••••• ••••••• Treatment of Rheumatoid arthritis, juvenile •••••••••••• ••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Tolmetin is a nonsteroidal anti-inflammatory agent. Studies in animals have shown tolmetin to possess anti-inflammatory, analgesic and antipyretic activity. In the rat, tolmetin prevents the development of experimentally induced polyarthritis and also decreases established inflammation. In patients with either rheumatoid arthritis or osteaoarthritis, tolmetin is as effective as aspirin and indomethacin in controlling disease activity, but the frequency of the milder gastrointestinal adverse effects and tinnitus was less than in aspirin-treated patients, and the incidence of central nervous system adverse effects was less than in indomethacin-treated patients. In patients with juvenile rheumatoid arthritis, tolmetin is as effective as aspirin in controlling disease activity, with a similar incidence of adverse reactions. tolmetin has produced additional therapeutic benefit when added to a regimen of gold salts and, to a lesser extent, with corticosteroids. Tolmetin should not be used in conjunction with salicylates since greater benefit from the combination is not likely, but the potential for adverse reactions is increased.
- Mechanism of action
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. Tolmetin does not appear to alter the course of the underlying disease in man.
Target Actions Organism AProstaglandin G/H synthase 2 inhibitorHumans UProstaglandin G/H synthase 1 inhibitorHumans - Absorption
Rapidly and almost completely absorbed with peak plasma levels being reached within 30-60 minutes after an oral therapeutic dose.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Essentially all of the administered dose is recovered in the urine in 24 hours either as an inactive oxidative metabolite or as conjugates of tolmetin.
Hover over products below to view reaction partners
- Route of elimination
Not Available
- Half-life
Biphasic elimination from the plasma consisting of a rapid phase with a half-life of one to 2 hours followed by a slower phase with a half-life of about 5 hours.
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain.
- Pathways
Pathway Category Tolmetin Action Pathway Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Tolmetin may decrease the excretion rate of Abacavir which could result in a higher serum level. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Tolmetin is combined with Abciximab. Acebutolol Tolmetin may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of adverse effects can be increased when Tolmetin is combined with Aceclofenac. Acemetacin The risk or severity of adverse effects can be increased when Tolmetin is combined with Acemetacin. - Food Interactions
- Avoid alcohol. Ingesting alcohol may increase the risk of developing an ulcer, or gastrointestinal bleed.
- Take with or without food. Food (or milk) can decrease oral bioavailability by 16%. Tolmetin may be taken with food to reduce gastrointestinal upset, but it may reduce tolmetin serum levels by 50%.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Tolmetin sodium WL259637KX 64490-92-2 QGUALMNFRILWRA-UHFFFAOYSA-M - Product Images
- International/Other Brands
- Tolectin (Teva) / Tolectin DS (Teva)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Tolectin 200 Tab 200mg Tablet 245 mg Oral Mcneil Pharmaceutical, Division Of Ortho Mcneil Inc. 1976-12-31 2002-08-02 Canada Tolectin 400 Cap 400mg Capsule 400 mg / cap Oral Mcneil Pharmaceutical, Division Of Ortho Mcneil Inc. 1980-12-31 2002-08-02 Canada Tolectin Tab 600mg Tablet 600 mg Oral Janssen Pharmaceuticals 1987-12-31 2006-02-27 Canada - Generic Prescription Products
Categories
- ATC Codes
- M01AB03 — Tolmetin
- M01AB — Acetic acid derivatives and related substances
- M01A — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
- M01 — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
- M — MUSCULO-SKELETAL SYSTEM
- Drug Categories
- Acetic Acid Derivatives and Related Substances
- Agents causing hyperkalemia
- Agents that produce hypertension
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)
- Antiinflammatory and Antirheumatic Products
- Antiinflammatory and Antirheumatic Products, Non-Steroids
- Antiinflammatory Preparations, Non-Steroids for Topical Use
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Enzyme Inhibitors
- Musculo-Skeletal System
- Nephrotoxic agents
- Non COX-2 selective NSAIDS
- OAT1/SLC22A6 inhibitors
- Peripheral Nervous System Agents
- Sensory System Agents
- Topical Products for Joint and Muscular Pain
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbonyl compounds
- Direct Parent
- Aryl-phenylketones
- Alternative Parents
- Benzoyl derivatives / Toluenes / N-methylpyrroles / Heteroaromatic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides show 1 more
- Substituents
- Aromatic heteromonocyclic compound / Aryl-phenylketone / Azacycle / Benzenoid / Benzoyl / Carboxylic acid / Carboxylic acid derivative / Heteroaromatic compound / Hydrocarbon derivative / Monocarboxylic acid or derivatives show 10 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- monocarboxylic acid, aromatic ketone, pyrroles (CHEBI:71941)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- D8K2JPN18B
- CAS number
- 26171-23-3
- InChI Key
- UPSPUYADGBWSHF-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- 2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetic acid
- SMILES
- CN1C(CC(O)=O)=CC=C1C(=O)C1=CC=C(C)C=C1
References
- General References
- TITCK Product Information: Tolectin (tolmetin) capsules for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0014643
- KEGG Compound
- C07149
- PubChem Compound
- 5509
- PubChem Substance
- 46507060
- ChemSpider
- 5308
- BindingDB
- 50295287
- 10636
- ChEBI
- 71941
- ChEMBL
- CHEMBL1020
- ZINC
- ZINC000000002191
- Therapeutic Targets Database
- DAP000777
- PharmGKB
- PA451721
- PDBe Ligand
- TLT
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Tolmetin
- PDB Entries
- 3s3g
- FDA label
- Download (77.4 KB)
- MSDS
- Download (44.3 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Ortho mcneil janssen pharmaceuticals inc
- Actavis elizabeth llc
- Ivax pharmaceuticals inc sub teva pharmaceuticals usa
- Mutual pharmaceutical co inc
- Mylan pharmaceuticals inc
- Sandoz inc
- Teva pharmaceuticals usa inc
- Packagers
- Amerisource Health Services Corp.
- DHHS Program Support Center Supply Service Center
- Dispensing Solutions
- Major Pharmaceuticals
- Murfreesboro Pharmaceutical Nursing Supply
- Mutual Pharmaceutical Co.
- Mylan
- Novopharm Ltd.
- Ortho-McNeil-Janssen Pharmaceuticals Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Pharmedix
- Physicians Total Care Inc.
- Qualitest
- Southwood Pharmaceuticals
- Teva Pharmaceutical Industries Ltd.
- United Research Laboratories Inc.
- Dosage Forms
Form Route Strength Capsule Oral 400 mg Capsule Oral Tablet Oral 245 mg Capsule Oral 400 mg / cap Tablet Oral 200 mg Tablet Oral 600 mg Capsule Oral 400 mg/1 Tablet Oral 200 mg/1 Tablet, film coated Oral 600 mg/1 - Prices
Unit description Cost Unit Tolectin 600 mg tablet 2.43USD tablet Tolmetin sodium 600 mg tablet 2.06USD tablet Tolmetin Sodium 400 mg capsule 1.77USD capsule Tolmetin sodium 200 mg tablet 0.77USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 156 dec °C PhysProp water solubility 222 mg/L Not Available logP 2.79 SANGSTER (1993) pKa 3.5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.131 mg/mL ALOGPS logP 2.81 ALOGPS logP 2.73 Chemaxon logS -3.3 ALOGPS pKa (Strongest Acidic) 3.93 Chemaxon pKa (Strongest Basic) -7.8 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 59.3 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 72.39 m3·mol-1 Chemaxon Polarizability 27.67 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9752 Blood Brain Barrier + 0.8387 Caco-2 permeable + 0.8867 P-glycoprotein substrate Non-substrate 0.7277 P-glycoprotein inhibitor I Non-inhibitor 0.9062 P-glycoprotein inhibitor II Non-inhibitor 0.9542 Renal organic cation transporter Non-inhibitor 0.7999 CYP450 2C9 substrate Non-substrate 0.7091 CYP450 2D6 substrate Non-substrate 0.7867 CYP450 3A4 substrate Non-substrate 0.6233 CYP450 1A2 substrate Non-inhibitor 0.9159 CYP450 2C9 inhibitor Non-inhibitor 0.9353 CYP450 2D6 inhibitor Non-inhibitor 0.9449 CYP450 2C19 inhibitor Non-inhibitor 0.9389 CYP450 3A4 inhibitor Non-inhibitor 0.9563 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9346 Ames test Non AMES toxic 0.8887 Carcinogenicity Non-carcinogens 0.8992 Biodegradation Ready biodegradable 0.5 Rat acute toxicity 2.9129 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9535 hERG inhibition (predictor II) Non-inhibitor 0.9545
Spectra
- Mass Spec (NIST)
- Download (9.07 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 175.1944883 predictedDarkChem Lite v0.1.0 [M-H]- 175.4485883 predictedDarkChem Lite v0.1.0 [M-H]- 162.24135 predictedDeepCCS 1.0 (2019) [M+H]+ 176.4244883 predictedDarkChem Lite v0.1.0 [M+H]+ 175.5828883 predictedDarkChem Lite v0.1.0 [M+H]+ 164.59935 predictedDeepCCS 1.0 (2019) [M+Na]+ 174.9032883 predictedDarkChem Lite v0.1.0 [M+Na]+ 174.9173883 predictedDarkChem Lite v0.1.0 [M+Na]+ 170.69249 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- Burdan F, Szumilo J, Klepacz R, Dudka J, Korobowicz A, Tokarska E, Cendrowska-Pinkosz M, Madej B, Klepacz L: Gastrointestinal and hepatic toxicity of selective and non-selective cyclooxygenase-2 inhibitors in pregnant and non-pregnant rats. Pharmacol Res. 2004 Nov;50(5):533-43. [Article]
- Capasso A, Sorrentino L: Arachidonic acid and its metabolites are involved in the expression of morphine dependence in guinea-pig isolated ileum. Eur J Pharmacol. 1997 Jul 9;330(2-3):199-204. [Article]
- Kirkova M, Alexandova A, Kesiova M, Todorov S: In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems. Comparison with non-selective and COX-2 selective NSAIDs. Auton Autacoid Pharmacol. 2007 Apr;27(2):99-104. [Article]
- Kennedy JH, Korn N, Thurston RJ: Prostaglandin levels in seminal plasma and sperm extracts of the domestic turkey, and the effects of cyclooxygenase inhibitors on sperm mobility. Reprod Biol Endocrinol. 2003 Oct 9;1:74. [Article]
- Capasso A: Further studies on the involvement of the arachidonic acid cascade in the acute dependence produced by mu, kappa and delta opioid agonists in isolated tissues. Neuropharmacology. 1999 Jun;38(6):871-7. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
- Gene Name
- PTGS1
- Uniprot ID
- P23219
- Uniprot Name
- Prostaglandin G/H synthase 1
- Molecular Weight
- 68685.82 Da
References
- Capasso A, Sorrentino L: Arachidonic acid and its metabolites are involved in the expression of morphine dependence in guinea-pig isolated ileum. Eur J Pharmacol. 1997 Jul 9;330(2-3):199-204. [Article]
- Kennedy JH, Korn N, Thurston RJ: Prostaglandin levels in seminal plasma and sperm extracts of the domestic turkey, and the effects of cyclooxygenase inhibitors on sperm mobility. Reprod Biol Endocrinol. 2003 Oct 9;1:74. [Article]
- Capasso A: Further studies on the involvement of the arachidonic acid cascade in the acute dependence produced by mu, kappa and delta opioid agonists in isolated tissues. Neuropharmacology. 1999 Jun;38(6):871-7. [Article]
- Burdan F, Szumilo J, Marzec B, Klepacz R, Dudka J: Skeletal developmental effects of selective and nonselective cyclooxygenase-2 inhibitors administered through organogenesis and fetogenesis in Wistar CRL:(WI)WUBR rats. Toxicology. 2005 Dec 15;216(2-3):204-23. Epub 2005 Sep 22. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Tryptophan 2,3-dioxygenase activity
- Specific Function
- Incorporates oxygen into the indole moiety of tryptophan. Has a broad specificity towards tryptamine and derivatives including D- and L-tryptophan, 5-hydroxytryptophan and serotonin (By similarity).
- Gene Name
- TDO2
- Uniprot ID
- P48775
- Uniprot Name
- Tryptophan 2,3-dioxygenase
- Molecular Weight
- 47871.215 Da
References
- Dairam A, Antunes EM, Saravanan KS, Daya S: Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels. Life Sci. 2006 Nov 10;79(24):2269-74. Epub 2006 Aug 1. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Peroxidase activity
- Specific Function
- Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production o...
- Gene Name
- MPO
- Uniprot ID
- P05164
- Uniprot Name
- Myeloperoxidase
- Molecular Weight
- 83867.71 Da
References
- Anderson R, Oosthuizen R, Grabow G: Prevention of peroxidase mediated inhibition of neutrophil motility and lymphocyte transformation by levamisole, OMPI, sodium aurothiomalate, indomethacin and tolmetin in vitro. Int J Immunopharmacol. 1981;3(2):123-32. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Ojingwa JC, Spahn-Langguth H, Benet LZ: Reversible binding of tolmetin, zomepirac, and their glucuronide conjugates to human serum albumin and plasma. J Pharmacokinet Biopharm. 1994 Feb;22(1):19-40. [Article]
- Borga O, Borga B: Serum protein binding of nonsteroidal antiinflammatory drugs: a comparative study. J Pharmacokinet Biopharm. 1997 Feb;25(1):63-77. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 03, 2023 23:48