Identification

Name
Tolmetin
Accession Number
DB00500  (APRD01268)
Type
Small Molecule
Groups
Approved
Description

A non-steroidal anti-inflammatory agent (anti-inflammatory agents, NON-steroidal) similar in mode of action to indomethacin. [PubChem]

Structure
Thumb
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
Product Ingredients
IngredientUNIICASInChI Key
Tolmetin sodiumWL259637KX64490-92-2QGUALMNFRILWRA-UHFFFAOYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tolectin 200 Tab 200mgTablet245 mgOralMcneil Pharmaceutical, Division Of Ortho Mcneil Inc.1976-12-312002-08-02Canada
Tolectin 400 Cap 400mgCapsule400 mgOralMcneil Pharmaceutical, Division Of Ortho Mcneil Inc.1980-12-312002-08-02Canada
Tolectin Tab 600mgTablet600 mgOralJanssen Pharmaceuticals1987-12-312006-02-27Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Novo-tolmetin Capsules 400mgCapsule400 mgOralNovopharm Limited1994-12-312005-08-10Canada
Tolmetin SodiumTablet, film coated600 mg/1OralPhysicians Total Care, Inc.1994-08-302009-06-30Us
Tolmetin SodiumTablet200 mg/1OralMutual Pharmaceutical2009-09-04Not applicableUs
Tolmetin SodiumCapsule400 mg/1OralMylan Pharmaceuticals1993-05-27Not applicableUs
Tolmetin SodiumCapsule400 mg/1OralTeva1991-12-012014-03-31Us
Tolmetin SodiumCapsule400 mg/1OralMutual Pharmaceutical2009-09-04Not applicableUs
Tolmetin SodiumCapsule400 mg/1OralPhysicians Total Care, Inc.1991-12-012002-06-30Us
Tolmetin SodiumTablet, film coated600 mg/1OralStat Rx USA2009-11-02Not applicableUs
Tolmetin SodiumCapsule400 mg/1OralTeva2012-07-262017-09-30Us00093 2075 01 nlmimage10 c326e187
Tolmetin SodiumTablet, film coated600 mg/1OralMylan Pharmaceuticals1994-08-30Not applicableUs
International/Other Brands
Tolectin (Teva) / Tolectin DS (Teva)
Categories
UNII
D8K2JPN18B
CAS number
26171-23-3
Weight
Average: 257.2845
Monoisotopic: 257.105193351
Chemical Formula
C15H15NO3
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

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.

Associated Conditions
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.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Human
UProstaglandin G/H synthase 1
inhibitor
Human
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.

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
Toxicity

Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Tolmetin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of gastrointestinal bleeding can be increased when Tolmetin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of gastrointestinal bleeding can be increased when Tolmetin is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of gastrointestinal bleeding can be increased when Tolmetin is combined with 4-hydroxycoumarin.
AbacavirTolmetin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Tolmetin is combined with Abciximab.
AcarboseTolmetin may decrease the excretion rate of Acarbose which could result in a higher serum level.
AcebutololTolmetin may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Tolmetin is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Tolmetin is combined with Acemetacin.
AcenocoumarolThe risk or severity of gastrointestinal bleeding can be increased when Tolmetin is combined with Acenocoumarol.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014643
KEGG Compound
C07149
PubChem Compound
5509
PubChem Substance
46507060
ChemSpider
5308
BindingDB
50295287
ChEBI
71941
ChEMBL
CHEMBL1020
Therapeutic Targets Database
DAP000777
PharmGKB
PA451721
HET
TLT
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tolmetin
ATC Codes
M01AB03 — TolmetinM02AA21 — Tolmetin
PDB Entries
3s3g
FDA label
Download (77.4 KB)
MSDS
Download (44.3 KB)

Clinical Trials

Clinical Trials
Not Available

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
FormRouteStrength
CapsuleOral400 mg
TabletOral245 mg
TabletOral600 mg
CapsuleOral400 mg/1
TabletOral200 mg/1
Tablet, film coatedOral600 mg/1
Prices
Unit descriptionCostUnit
Tolectin 600 mg tablet2.43USD tablet
Tolmetin sodium 600 mg tablet2.06USD tablet
Tolmetin Sodium 400 mg capsule1.77USD capsule
Tolmetin sodium 200 mg tablet0.77USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)156 dec °CPhysProp
water solubility222 mg/LNot Available
logP2.79SANGSTER (1993)
pKa3.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.131 mg/mLALOGPS
logP2.81ALOGPS
logP2.73ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)3.96ChemAxon
pKa (Strongest Basic)-7.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area59.3 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity72.39 m3·mol-1ChemAxon
Polarizability27.67 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9752
Blood Brain Barrier+0.8387
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.7277
P-glycoprotein inhibitor INon-inhibitor0.9062
P-glycoprotein inhibitor IINon-inhibitor0.9542
Renal organic cation transporterNon-inhibitor0.7999
CYP450 2C9 substrateNon-substrate0.7091
CYP450 2D6 substrateNon-substrate0.7867
CYP450 3A4 substrateNon-substrate0.6233
CYP450 1A2 substrateNon-inhibitor0.9159
CYP450 2C9 inhibitorNon-inhibitor0.9353
CYP450 2D6 inhibitorNon-inhibitor0.9449
CYP450 2C19 inhibitorNon-inhibitor0.9389
CYP450 3A4 inhibitorNon-inhibitor0.9563
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9346
Ames testNon AMES toxic0.8887
CarcinogenicityNon-carcinogens0.8992
BiodegradationReady biodegradable0.5
Rat acute toxicity2.9129 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9535
hERG inhibition (predictor II)Non-inhibitor0.9545
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.07 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-0090000000-5053b1021a81c4668b54
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0910000000-7cb6eb9d5a42f35eb4bc
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0900000000-9898c207cc31a596d319
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014l-6900000000-439955132bb3d3d37cf7
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9200000000-aed48305fd97ea83af6d
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-014i-1900000000-3399455ef4fbd98a64d3

Taxonomy

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
Aryl-phenylketone / Benzoyl / Toluene / Monocyclic benzene moiety / N-methylpyrrole / Substituted pyrrole / Benzenoid / Pyrrole / Heteroaromatic compound / Carboxylic acid derivative
show 10 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monocarboxylic acid, aromatic ketone, pyrroles (CHEBI:71941)

Targets

Kind
Protein
Organism
Human
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
  1. 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. [PubMed:15458776]
  2. 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. [PubMed:9253954]
  3. 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. [PubMed:17391279]
  4. 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. [PubMed:14613550]
  5. 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. [PubMed:10465690]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:9253954]
  2. 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. [PubMed:14613550]
  3. 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. [PubMed:10465690]
  4. 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. [PubMed:16182428]

Enzymes

Kind
Protein
Organism
Human
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
  1. 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. [PubMed:16952380]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:6266970]

Carriers

Kind
Protein
Organism
Human
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
  1. 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. [PubMed:8027947]
  2. Borga O, Borga B: Serum protein binding of nonsteroidal antiinflammatory drugs: a comparative study. J Pharmacokinet Biopharm. 1997 Feb;25(1):63-77. [PubMed:9353694]

Transporters

Kind
Protein
Organism
Human
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
  1. 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. [PubMed:10220563]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:39