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Identification
NameMefenamic acid
Accession NumberDB00784  (APRD00730)
Typesmall molecule
Groupsapproved
Description

A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
Acide méfénamiqueFrenchDCF
Acido mefenamicoSpanishINN
Acidum mefenamicumLatinINN
MefenaminsäureGermanINN
SaltsNot Available
Brand names
NameCompany
CoslanParke Davis
LysalgoSIT
MefacitSecFarm
ParkemedPfizer
PonalarCoronet Crown
PonstanPfizer
Ponstan FortePfizer
PonstelAdcock Ingram Pharmaceuticals
PonstylPfizer
Ponstyl FortPfizer
PontalDaiichi Sankyo
TanstonPfizer
Brand mixtures
Brand NameIngredients
MeparMefenamic Acid and Paracetamol
ParaspasMefenamic Acid and Dicycloverine
Reotran-MFMefenamic Acid and Tranexamic Acid
Categories
CAS number61-68-7
WeightAverage: 241.2851
Monoisotopic: 241.110278729
Chemical FormulaC15H15NO2
InChI KeyHYYBABOKPJLUIN-UHFFFAOYSA-N
InChI
InChI=1S/C15H15NO2/c1-10-6-5-9-13(11(10)2)16-14-8-4-3-7-12(14)15(17)18/h3-9,16H,1-2H3,(H,17,18)
IUPAC Name
2-[(2,3-dimethylphenyl)amino]benzoic acid
SMILES
CC1=C(C)C(NC2=CC=CC=C2C(O)=O)=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzoic Acid and Derivatives
Direct parentAminobenzoic Acid Derivatives
Alternative parentsBenzoic Acids; Benzoyl Derivatives; Toluenes; Polyamines; Carboxylic Acids; Secondary Amines; Enolates
Substituentsbenzoyl; toluene; secondary amine; carboxylic acid derivative; enolate; carboxylic acid; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the aminobenzoic acid derivatives. These are benzoic acids (or derivative thereof) containing an amine group attached to the benzene moiety.
Pharmacology
IndicationFor the treatment of rheumatoid arthritis, osteoarthritis, dysmenorrhea, and mild to moderate pain, inflammation, and fever.
PharmacodynamicsMefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). It exhibits anti-inflammatory, analgesic, and antipyretic activities. Similar to other NSAIDs, mefenamic acid inhibits prostaglandin synthetase.
Mechanism of actionMefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced.
AbsorptionMefenamic acid is rapidly absorbed after oral administration.
Volume of distribution
  • 1.06 L/kg [Normal Healthy Adults (18-45 yr)]
Protein binding90%
Metabolism

Mefenamic acid undergoes metabolism by CYP2C9 to 3-hydroxymethyl mefenamic acid, and further oxidation to a 3-carboxymefenamic acid may occur. The activity of these metabolites has not been studied. Mefenamic acid is also glucuronidated directly.

Route of eliminationThe fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3-carboxymefenamic acid.3 The elimination half-life of mefenamic acid is approximately two hours. Mefenamic acid, its metabolites and conjugates are primarily excreted by the kidneys. Both renal and hepatic excretion are significant pathways of elimination.
Half life2 hours
Clearance
  • Oral cl=21.23 L/hr [Healthy adults (18-45 yrs)]
ToxicityOral, rat LD50: 740 mg/kg. Symptoms of overdose may include severe stomach pain, coffee ground-like vomit, dark stool, ringing in the ears, change in amount of urine, unusually fast or slow heartbeat, muscle weakness, slow or shallow breathing, confusion, severe headache or loss of consciousness.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Mefenamic Acid Action PathwayDrug actionSMP00109
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9156
Blood Brain Barrier + 0.762
Caco-2 permeable + 0.8866
P-glycoprotein substrate Non-substrate 0.7948
P-glycoprotein inhibitor I Non-inhibitor 0.8632
P-glycoprotein inhibitor II Non-inhibitor 0.9147
Renal organic cation transporter Non-inhibitor 0.9191
CYP450 2C9 substrate Non-substrate 0.6814
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.7019
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Inhibitor 0.8949
CYP450 2D6 substrate Non-inhibitor 0.9483
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9175
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6613
Ames test Non AMES toxic 0.812
Carcinogenicity Non-carcinogens 0.5833
Biodegradation Not ready biodegradable 0.822
Rat acute toxicity 2.5445 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9727
hERG inhibition (predictor II) Non-inhibitor 0.8706
Pharmacoeconomics
Manufacturers
  • Shionogi pharma inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
Prices
Unit descriptionCostUnit
Ponstel 250 mg capsule11.85USDcapsule
Mefenamic acid powder2.85USDg
Ponstel 250 mg kapseals1.59USDeach
Apo-Mefenamic 250 mg Capsule0.52USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point230-231 °CPhysProp
water solubility20 mg/L (at 30 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP5.12HANSCH,C ET AL. (1995)
logS-3.78ADME Research, USCD
pKa4.2SANGSTER (1994)
Predicted Properties
PropertyValueSource
water solubility1.37e-02 g/lALOGPS
logP4.58ALOGPS
logP5.4ChemAxon
logS-4.2ALOGPS
pKa (strongest acidic)3.89ChemAxon
pKa (strongest basic)-1.6ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count2ChemAxon
polar surface area49.33ChemAxon
rotatable bond count3ChemAxon
refractivity71.88ChemAxon
polarizability26.22ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00151
KEGG CompoundC02168
PubChem Compound4044
PubChem Substance46505405
ChemSpider3904
BindingDB50134036
Therapeutic Targets DatabaseDAP000779
PharmGKBPA450347
IUPHAR2593
Guide to Pharmacology2593
Drug Product Database2237826
RxListhttp://www.rxlist.com/cgi/generic3/mefenamic.htm
Drugs.comhttp://www.drugs.com/cdi/mefenamic-acid.html
WikipediaMefenamic_acid
ATC CodesM01AG01
AHFS Codes
  • 28:08.04.92
PDB EntriesNot Available
FDA labelshow(135 KB)
MSDSshow(59.7 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolThe NSAID, mefanamic acid, may increase the anticoagulant effect of acenocoumarol.
AlendronateIncreased risk of gastric toxicity
AnisindioneThe NSAID, mefanamic acid, may increase the anticoagulant effect of anisindione.
Azilsartan medoxomilIncreases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
ColesevelamBile acid sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Monitor for decreased serum concentrations/therapeutic effects of nonsteroidal anti-inflammatory agents (NSAID) if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.
CyclosporineMonitor for nephrotoxicity
DicoumarolThe NSAID, mefanamic acid, may increase the anticoagulant effect of dicumarol.
EltrombopagIncreases levels of Mefenamic acid via metabolism decrease. UDP-glucuronosyltransferase inhibition with unclear significance.
LithiumThe NSAID, mefenamic acid, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
MethotrexateThe NSAID, mefenamic acid, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
TamoxifenMefenamic acid may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Mefenamic acid is initiated, discontinued or dose changed.
TolbutamideMefanamic acid, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Mefanamic acid is initiated, discontinued or dose changed.
TorasemideMefanamic acid, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Mefanamic acid is initiated, discontinued or dose changed.
TrandolaprilThe NSAID, Mefenamic acid, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Mefenamic acid is initiated, discontinued or dose changed.
TreprostinilThe prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Mefenamic acid. Monitor for increased bleeding during concomitant thearpy.
TrimethoprimThe strong CYP2C9 inhibitor, Mefenamic acid, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Mefenamic acid is initiated, discontinued or dose changed.
VoriconazoleMefanamic acid, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if mefanamic acid is initiated, discontinued or dose changed.
WarfarinMefenamic acid, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. The antiplatelet effect of mefenamic acid may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if mefenamic acid is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol.
  • Take with food.

Targets

1. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Gierse JK, Hauser SD, Creely DP, Koboldt C, Rangwala SH, Isakson PC, Seibert K: Expression and selective inhibition of the constitutive and inducible forms of human cyclo-oxygenase. Biochem J. 1995 Jan 15;305 ( Pt 2):479-84. Pubmed
  2. Bhat AS, Tandan SK, Kumar D, Krishna V, Prakash VR: Interaction between inhibitors of inducible nitric oxide synthase and cyclooxygenase in adjuvant-induced arthritis in female albino rats: an isobolographic study. Eur J Pharmacol. 2007 Feb 5;556(1-3):190-9. Epub 2006 Oct 27. Pubmed
  3. Bhat AS, Tandan SK, Kumar D, Krishna V, Prakash VR: Interaction between inhibitors of inducible nitric oxide synthase and cyclooxygenase in Brewer’s yeast induced pyrexia in mice: an isobolographic study. Eur J Pharmacol. 2005 Mar 28;511(2-3):137-42. Pubmed
  4. Cryer B, Feldman M: Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998 May;104(5):413-21. Pubmed
  5. Walton LJ, Franklin IJ, Bayston T, Brown LC, Greenhalgh RM, Taylor GW, Powell JT: Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms. Circulation. 1999 Jul 6;100(1):48-54. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

  1. Sinniah R, Lye WC: Acute renal failure from hemoglobinuric and interstitial nephritis secondary to iodine and mefenamic acid. Clin Nephrol. 2001 Mar;55(3):254-8. Pubmed
  2. Joo Y, Kim HS, Woo RS, Park CH, Shin KY, Lee JP, Chang KA, Kim S, Suh YH: Mefenamic acid shows neuroprotective effects and improves cognitive impairment in in vitro and in vivo Alzheimer’s disease models. Mol Pharmacol. 2006 Jan;69(1):76-84. Epub 2005 Oct 13. Pubmed
  3. Cryer B, Feldman M: Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998 May;104(5):413-21. Pubmed
  4. Gierse JK, Hauser SD, Creely DP, Koboldt C, Rangwala SH, Isakson PC, Seibert K: Expression and selective inhibition of the constitutive and inducible forms of human cyclo-oxygenase. Biochem J. 1995 Jan 15;305 ( Pt 2):479-84. Pubmed
  5. Laudanno OM, Cesolari JA, Esnarriaga J, Flaherty P, Vada J, Guastalli G, San Miguel P, Bedini OA: [In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1-COX-2 and gastrointestinal ulcers, in rats] Acta Gastroenterol Latinoam. 1998;28(3):249-55. Pubmed

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on November 24, 2013 14:27