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Identification
NameDiclofenac
Accession NumberDB00586  (APRD00527)
Typesmall molecule
Groupsapproved
Description

A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
Diclofenac AcidNot AvailableNot Available
ISV-205Not AvailableNot Available
Salts
Name/CAS Structure Properties
Diclofenac potassium
Thumb Not applicable DBSALT000864
Diclofenac sodium
15307-79-6
Thumb
  • InChI Key: KPHWPUGNDIVLNH-UHFFFAOYSA-M
  • Monoisotopic Mass: 316.998628658
  • Average Mass: 318.13
DBSALT000466
Brand names
NameCompany
AclonacNot Available
AllvoranNot Available
CataflamNot Available
DylojectNot Available
EcofenacNot Available
EffektonNot Available
Nu-DicloNot Available
PennsaidNot Available
PrimofenacNot Available
ProphenatinNot Available
RhumalganNot Available
SolarazeNot Available
VoltarenNot Available
Voltaren EmulgelNot Available
VoltarolNot Available
Brand mixturesNot Available
Categories
CAS number15307-86-5
WeightAverage: 296.149
Monoisotopic: 295.016684015
Chemical FormulaC14H11Cl2NO2
InChI KeyInChIKey=DCOPUUMXTXDBNB-UHFFFAOYSA-N
InChI
InChI=1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)
IUPAC Name
2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid
SMILES
OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenylacetic Acid Derivatives
Direct parentPhenylacetic Acid Derivatives
Alternative parentsDichlorobenzenes; Aryl Chlorides; Enolates; Secondary Amines; Carboxylic Acids; Polyamines; Organochlorides
Substituents1,3-dichlorobenzene; chlorobenzene; aryl halide; aryl chloride; enolate; polyamine; secondary amine; carboxylic acid derivative; carboxylic acid; amine; organohalogen; organonitrogen compound; organochloride
Classification descriptionThis compound belongs to the phenylacetic acid derivatives. These are compounds containing a phenylacetic acid moiety, which consists of a phenyl group substituted at the second position by an acetic acid.
Pharmacology
IndicationFor the acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis.
PharmacodynamicsDiclofenac is an acetic acid nonsteroidal antiinflammatory drug (NSAID) with analgesic and antipyretic properties. Diclofenac is used to treat pain, dysmenorrhea, ocular inflammation, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and actinic keratosis
Mechanism of actionThe antiinflammatory effects of diclofenac are believed to be due to inhibition of both leukocyte migration and the enzyme cylooxygenase (COX-1 and COX-2), leading to the peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, inhibition of their synthesis is responsible for the analgesic effects of diclofenac. Antipyretic effects may be due to action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat dissipation.
AbsorptionCompletely absorbed from the gastrointestinal tract.
Volume of distribution
  • 1.3 L/kg
Protein bindingMore than 99%
Metabolism

Hepatic

SubstrateEnzymesProduct
Diclofenac
4'-HydroxydiclofenacDetails
Diclofenac
Diclofenac acyl glucuronideDetails
Diclofenac
3'-HydroxydiclofenacDetails
Diclofenac
5-HydroxydiclofenacDetails
4'-Hydroxydiclofenac
    4',5-DihydroxydiclofenacDetails
    5-Hydroxydiclofenac
      4',5-DihydroxydiclofenacDetails
      Route of eliminationDiclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites.
      Half life2 hours
      Clearance
      • oral cl=622 mL/min [healthy]
      • renal cl <1 mL/min [healthy]
      ToxicitySymptoms of overdose include loss of consciousness, increased intracranial pressure, and aspiration pneumonitis. LD50=390mg/kg (orally in mice)
      Affected organisms
      • Humans and other mammals
      Pathways
      PathwayCategorySMPDB ID
      Diclofenac Action PathwayDrug actionSMP00093
      SNP Mediated EffectsNot Available
      SNP Mediated Adverse Drug ReactionsNot Available
      ADMET
      Predicted ADMET features
      Property Value Probability
      Human Intestinal Absorption + 0.9548
      Blood Brain Barrier + 0.9541
      Caco-2 permeable + 0.8867
      P-glycoprotein substrate Non-substrate 0.7976
      P-glycoprotein inhibitor I Non-inhibitor 0.8254
      P-glycoprotein inhibitor II Non-inhibitor 0.9548
      Renal organic cation transporter Non-inhibitor 0.9086
      CYP450 2C9 substrate Non-substrate 0.7779
      CYP450 2D6 substrate Non-substrate 0.9116
      CYP450 3A4 substrate Non-substrate 0.6724
      CYP450 1A2 substrate Inhibitor 0.5923
      CYP450 2C9 substrate Inhibitor 0.6786
      CYP450 2D6 substrate Non-inhibitor 0.848
      CYP450 2C19 substrate Non-inhibitor 0.8947
      CYP450 3A4 substrate Non-inhibitor 0.8647
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6607
      Ames test Non AMES toxic 0.9133
      Carcinogenicity Non-carcinogens 0.6706
      Biodegradation Not ready biodegradable 0.9719
      Rat acute toxicity 3.6447 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.9514
      hERG inhibition (predictor II) Non-inhibitor 0.868
      Pharmacoeconomics
      Manufacturers
      • Institut biochemique sa
      • Xanodyne pharmaceutics inc
      • Nautilus neurosciences inc
      • Novartis pharmaceuticals corp
      • Apotex inc
      • Mutual pharmaceutical co inc
      • Mylan pharmaceuticals inc
      • Sandoz inc
      • Teva pharmaceuticals usa inc
      • Watson laboratories inc
      • Nycomed us inc
      • Novartis consumer health inc
      • Akorn inc
      • Alcon inc
      • Apotex inc richmond hill
      • Bausch and lomb inc
      • Falcon pharmaceuticals ltd
      • Nexus pharmaceuticals inc
      • Mallinckrodt inc
      • Actavis elizabeth llc
      • Alphapharm party ltd
      • Carlsbad technology inc
      • Nostrum laboratories inc
      • Pliva inc
      • Roxane laboratories inc
      • Teva pharmaceuticals usa
      • Unique pharmaceutical laboratories
      • Biovail laboratories inc
      • Dexcel ltd
      Packagers
      Dosage forms
      FormRouteStrength
      SolutionOphthalmic
      SolutionTopical
      SuppositoryRectal
      TabletOral
      Tablet, coatedOral
      Tablet, extended releaseOral
      Prices
      Unit descriptionCostUnit
      Voltaren Ophtha 0.1 % Solution2.73USDml
      Voltaren 100 mg Suppository1.88USDsuppository
      Voltaren Sr 100 mg Sustained-Release Tablet1.86USDtablet
      Voltaren 50 mg Suppository1.4USDsuppository
      Voltaren Sr 75 mg Sustained-Release Tablet1.31USDtablet
      Voltaren 50 mg Enteric-Coated Tablet0.93USDtablet
      Pms-Diclofenac 100 mg Suppository0.88USDsuppository
      Sandoz Diclofenac 100 mg Suppository0.88USDsuppository
      Novo-Difenac Sr 100 mg Sustained-Release Tablet0.8USDtablet
      Pms-Diclofenac-Sr 100 mg Sustained-Release Tablet0.8USDtablet
      Sandoz Diclofenac Sr 100 mg Sustained-Release Tablet0.8USDtablet
      Pms-Diclofenac 50 mg Suppository0.65USDsuppository
      Sandoz Diclofenac 50 mg Suppository0.65USDsuppository
      Novo-Difenac Sr 75 mg Sustained-Release Tablet0.6USDtablet
      Pms-Diclofenac-Sr 75 mg Sustained-Release Tablet0.6USDtablet
      Sandoz Diclofenac Sr 75 mg Sustained-Release Tablet0.6USDtablet
      Apo-Diclo 50 mg Enteric-Coated Tablet0.4USDtablet
      Novo-Difenac 50 mg Enteric-Coated Tablet0.4USDtablet
      Pms-Diclofenac 50 mg Enteric-Coated Tablet0.4USDtablet
      Sandoz Diclofenac 50 mg Enteric-Coated Tablet0.4USDtablet
      Apo-Diclo 25 mg Enteric-Coated Tablet0.2USDtablet
      Novo-Difenac 25 mg Enteric-Coated Tablet0.2USDtablet
      Nu-Diclo 25 mg Enteric-Coated Tablet0.2USDtablet
      Pms-Diclofenac 25 mg Enteric-Coated Tablet0.2USDtablet
      Sandoz Diclofenac 25 mg Enteric-Coated Tablet0.2USDtablet
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      Patents
      CountryPatent NumberApprovedExpires (estimated)
      United States76628582009-02-242029-02-24
      United States56076901994-04-132014-04-13
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      melting point283-285 °CNot Available
      water solubility2.37 mg/L (at 25 °C)FINI,A ET AL. (1986)
      logP4.51AVDEEF,A (1997)
      pKa4.15SANGSTER (1994)
      Predicted Properties
      PropertyValueSource
      water solubility4.47e-03 g/lALOGPS
      logP4.98ALOGPS
      logP4.26ChemAxon
      logS-4.8ALOGPS
      pKa (strongest acidic)4ChemAxon
      pKa (strongest basic)-2.1ChemAxon
      physiological charge-1ChemAxon
      hydrogen acceptor count3ChemAxon
      hydrogen donor count2ChemAxon
      polar surface area49.33ChemAxon
      rotatable bond count4ChemAxon
      refractivity75.46ChemAxon
      polarizability27.93ChemAxon
      number of rings2ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterYesChemAxon
      Veber's ruleNoChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis Reference

      Takuzo Kamishita, “Gel preparations for topical application of diclofenac sodium.” U.S. Patent US4670254, issued October, 1983.

      US4670254
      General Reference
      1. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C: Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006 Jun 3;332(7553):1302-8. Pubmed
      2. Solomon DH, Avorn J, Sturmer T, Glynn RJ, Mogun H, Schneeweiss S: Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk. Arthritis Rheum. 2006 May;54(5):1378-89. Pubmed
      3. FitzGerald GA, Patrono C: The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001 Aug 9;345(6):433-42. Pubmed
      4. Graham DJ: COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense. JAMA. 2006 Oct 4;296(13):1653-6. Epub 2006 Sep 12. Pubmed
      5. Brater DC: Renal effects of cyclooxygyenase-2-selective inhibitors. J Pain Symptom Manage. 2002 Apr;23(4 Suppl):S15-20; discussion S21-3. Pubmed
      6. Sigma Aldrich Link
      7. Gan TJ: Diclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin. 2010 Jul;26(7):1715-31. Pubmed
      External Links
      ResourceLink
      KEGG CompoundC01690
      PubChem Compound3033
      PubChem Substance46504644
      ChemSpider2925
      BindingDB13066
      ChEBI4507
      ChEMBLCHEMBL139
      Therapeutic Targets DatabaseDAP000620
      PharmGKBPA449293
      IUPHAR2714
      Guide to Pharmacology2714
      HETDIF
      Drug Product Database2241225
      RxListhttp://www.rxlist.com/cgi/generic/diclofen.htm
      Drugs.comhttp://www.drugs.com/cdi/diclofenac-drops.html
      WikipediaDiclofenac
      ATC CodesM01AB05M02AA15S01BC03D11AX18
      AHFS Codes
      • 28:08.04.92
      • 28:08.04.08
      PDB EntriesNot Available
      FDA labelshow(37.5 KB)
      MSDSshow(73.6 KB)
      Interactions
      Drug Interactions
      Drug
      AlendronateIncreased risk of gastric toxicity
      AnisindioneThe NSAID, diclofenac, 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, diclofenac, may increase the anticoagulant effect of dicumarol.
      DifluprednateNSAIDs may slow healing.
      EltrombopagEltrombopag increases levels of Diclofenac via metabolism decrease. UDP-glucuronosyltransferase inhibition.
      Ginkgo bilobaAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
      LithiumThe NSAID, diclofenac, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
      MethotrexateThe NSAID, diclofenac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
      PralatrexateNSAIDs increase the risk of toxicity due to impairment of renal clearance of pralatrexate thus increasing exposure. Monitor for adverse effects or adjust dose of pralatrexate.
      RifampicinRifampin, a CYP2C9 inducer, may increase the metabolism of diclofenac.
      TacrineThe metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Diclofenac, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Diclofenac is initiated, discontinued or if the dose is changed.
      TelmisartanConcomitant use of Telmisartan and Diclofenac may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
      TimololThe NSAID, Diclofenac, may antagonize the antihypertensive effect of Timolol.
      TizanidineDiclofenac may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
      TrandolaprilThe NSAID, Diclofenac, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Diclofenac is initiated, discontinued or dose changed.
      TreprostinilThe prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Diclofenac. Monitor for increased bleeding during concomitant thearpy.
      VilazodoneIncreased risk of bleeding with concomitant use of NSAIDs with vilazodone.
      VoriconazoleVoriconazole, a strong CYP2C9 inhibitor, may increase the serum concentration of diclofenac by decreasing its metabolism. Renal impairment may increase the risk of diclofenac adverse effects. Monitor for changes in therapeutic and adverse effects of diclofenac if voriconazole is initiated, discontinued or dose changed.
      WarfarinThe antiplatelet effects of oral diclofenac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.
      Food Interactions
      • Avoid alcohol.
      • Take with food to reduce irritation.

      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. Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol. 2003 Jan;55(1):51-61. Pubmed
      2. Blomme EA, Chinn KS, Hardy MM, Casler JJ, Kim SH, Opsahl AC, Hall WA, Trajkovic D, Khan KN, Tripp CS: Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice. Br J Dermatol. 2003 Feb;148(2):211-23. Pubmed
      3. Beubler E: [Pharmacology of cyclooxygenase 2 inhibition] Wien Med Wochenschr. 2003;153(5-6):95-9. Pubmed
      4. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. Pubmed
      5. Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, Stallings WC, Kurumbail RG, Marnett LJ: A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem. 2003 Nov 14;278(46):45763-9. Epub 2003 Aug 18. Pubmed

      2. Prostaglandin G/H synthase 1

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: inhibitor

      Components

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

      References:

      1. Calkin AC, Sudhir K, Honisett S, Williams MR, Dawood T, Komesaroff PA: Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2. J Clin Endocrinol Metab. 2002 Nov;87(11):5072-5. Pubmed
      2. Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol. 2003 Jan;55(1):51-61. Pubmed
      3. Kampfer H, Brautigam L, Geisslinger G, Pfeilschifter J, Frank S: Cyclooxygenase-1-coupled prostaglandin biosynthesis constitutes an essential prerequisite for skin repair. J Invest Dermatol. 2003 May;120(5):880-90. Pubmed
      4. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. Pubmed
      5. Hinz B, Rau T, Auge D, Werner U, Ramer R, Rietbrock S, Brune K: Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003 Sep;74(3):222-35. Pubmed
      6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

      3. Arachidonate 5-lipoxygenase

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: potentiator

      Components

      Name UniProt ID Details
      Arachidonate 5-lipoxygenase P09917 Details

      References:

      1. Charlier C, Michaux C: Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur J Med Chem. 2003 Jul-Aug;38(7-8):645-59. Pubmed
      2. Kudo C, Kori M, Matsuzaki K, Yamai K, Nakajima A, Shibuya A, Niwa H, Kamisaki Y, Wada K: Diclofenac inhibits proliferation and differentiation of neural stem cells. Biochem Pharmacol. 2003 Jul 15;66(2):289-95. Pubmed
      3. Whittle BJ: Cyclooxygenase and nitric oxide systems in the gut as therapeutic targets for safer anti-inflammatory drugs. Curr Opin Pharmacol. 2004 Dec;4(6):538-45. Pubmed

      4. Sodium channel protein type 4 subunit alpha

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Sodium channel protein type 4 subunit alpha P35499 Details

      References:

      1. Yang YC, Kuo CC: An inactivation stabilizer of the Na+ channel acts as an opportunistic pore blocker modulated by external Na+. J Gen Physiol. 2005 May;125(5):465-81. Epub 2005 Apr 11. Pubmed
      2. Voilley N: Acid-sensing ion channels (ASICs): new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs). Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):71-9. Pubmed
      3. Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB: Acid-induced pain and its modulation in humans. J Neurosci. 2004 Dec 1;24(48):10974-9. Pubmed

      5. Acid-sensing ion channel 1

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Acid-sensing ion channel 1 P78348 Details

      References:

      1. Voilley N, de Weille J, Mamet J, Lazdunski M: Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci. 2001 Oct 15;21(20):8026-33. Pubmed

      6. Potassium voltage-gated channel subfamily KQT member 2

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: other

      Components

      Name UniProt ID Details
      Potassium voltage-gated channel subfamily KQT member 2 O43526 Details

      References:

      1. Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B: Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005 Apr;67(4):1053-66. Epub 2004 Dec 14. Pubmed
      2. Xiong Q, Gao Z, Wang W, Li M: Activation of Kv7 (KCNQ) voltage-gated potassium channels by synthetic compounds. Trends Pharmacol Sci. 2008 Feb;29(2):99-107. Epub 2008 Jan 18. Pubmed

      7. Potassium voltage-gated channel subfamily KQT member 3

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: other

      Components

      Name UniProt ID Details
      Potassium voltage-gated channel subfamily KQT member 3 O43525 Details

      References:

      1. Xiong Q, Gao Z, Wang W, Li M: Activation of Kv7 (KCNQ) voltage-gated potassium channels by synthetic compounds. Trends Pharmacol Sci. 2008 Feb;29(2):99-107. Epub 2008 Jan 18. Pubmed
      2. Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B: Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005 Apr;67(4):1053-66. Epub 2004 Dec 14. Pubmed

      8. Phospholipase A2, membrane associated

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Phospholipase A2, membrane associated P14555 Details

      References:

      1. Madanick RD, O’Loughlin CJ, Barkin JS: Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Dig Dis Sci. 2005 May;50(5):879-81. Pubmed
      2. Singh N, Jabeen T, Sharma S, Somvanshi RK, Dey S, Srinivasan A, Singh TP: Specific binding of non-steroidal anti-inflammatory drugs (NSAIDs) to phospholipase A2: structure of the complex formed between phospholipase A2 and diclofenac at 2.7 A resolution. Acta Crystallogr D Biol Crystallogr. 2006 Apr;62(Pt 4):410-6. Epub 2006 Mar 18. Pubmed
      3. Makela A, Kuusi T, Schroder T: Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. Scand J Clin Lab Invest. 1997 Aug;57(5):401-7. Pubmed

      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. Mo SL, Zhou ZW, Yang LP, Wei MQ, Zhou SF: New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126. Pubmed
      2. 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
      3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      4. 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
      5. Obach RS, Reed-Hagen AE: Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metab Dispos. 2002 Jul;30(7):831-7. Pubmed
      6. Leemann T, Transon C, Dayer P: Cytochrome P450TB (CYP2C): a major monooxygenase catalyzing diclofenac 4’-hydroxylation in human liver. Life Sci. 1993;52(1):29-34. Pubmed

      2. Cytochrome P450 2C19

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 2C19 P33261 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

      3. Cytochrome P450 1A2

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Cytochrome P450 1A2 P05177 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

      4. Cytochrome P450 2C8

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      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

      5. UDP-glucuronosyltransferase 1-1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      UDP-glucuronosyltransferase 1-1 P22309 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

      6. UDP-glucuronosyltransferase 2B7

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      UDP-glucuronosyltransferase 2B7 P16662 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

      7. Prostaglandin G/H synthase 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Prostaglandin G/H synthase 1 P23219 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

      8. Cytochrome P450 3A4

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 3A4 P08684 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

      9. Cytochrome P450 1A1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 1A1 P04798 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

      10. Cytochrome P450 2B6

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 2B6 P20813 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

      11. Cytochrome P450 2C18

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 2C18 P33260 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

      12. Cytochrome P450 2E1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Cytochrome P450 2E1 P05181 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

      1. Transthyretin

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Components

      Name UniProt ID Details
      Transthyretin P02766 Details

      References:

      1. Miller SR, Sekijima Y, Kelly JW: Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Lab Invest. 2004 May;84(5):545-52. Pubmed
      2. Almeida MR, Macedo B, Cardoso I, Alves I, Valencia G, Arsequell G, Planas A, Saraiva MJ: Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative. Biochem J. 2004 Jul 15;381(Pt 2):351-6. Pubmed

      2. Serum albumin

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Components

      Name UniProt ID Details
      Serum albumin P02768 Details

      References:

      1. Yamasaki K, Rahman MH, Tsutsumi Y, Maruyama T, Ahmed S, Kragh-Hansen U, Otagiri M: Circular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen. AAPS PharmSciTech. 2000 May 14;1(2):E12. Pubmed

      1. Multidrug resistance-associated protein 4

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Multidrug resistance-associated protein 4 O15439 Details

      References:

      1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. Pubmed

      2. Multidrug resistance protein 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Multidrug resistance protein 1 P08183 Details

      References:

      1. Wang E, Lew K, Barecki M, Casciano CN, Clement RP, Johnson WW: Quantitative distinctions of active site molecular recognition by P-glycoprotein and cytochrome P450 3A4. Chem Res Toxicol. 2001 Dec;14(12):1596-603. Pubmed

      3. Multidrug resistance-associated protein 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Multidrug resistance-associated protein 1 P33527 Details

      References:

      1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. Pubmed

      4. Solute carrier family 22 member 6

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 22 member 6 Q4U2R8 Details

      References:

      1. Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. Pubmed
      2. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. Pubmed
      3. 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

      5. Solute carrier family 22 member 8

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 22 member 8 Q8TCC7 Details

      References:

      1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. Pubmed

      6. Solute carrier organic anion transporter family member 1C1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 1C1 Q9NYB5 Details

      References:

      1. Westholm DE, Stenehjem DD, Rumbley JN, Drewes LR, Anderson GW: Competitive inhibition of organic anion transporting polypeptide 1c1-mediated thyroxine transport by the fenamate class of nonsteroidal antiinflammatory drugs. Endocrinology. 2009 Feb;150(2):1025-32. Epub 2008 Oct 9. Pubmed
      2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

      7. Solute carrier family 22 member 11

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 22 member 11 Q9NSA0 Details

      References:

      1. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. Pubmed

      Comments
      Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11