Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
Identification
NameValdecoxib
Accession NumberDB00580  (APRD00183, DB07576)
Typesmall molecule
Groupsinvestigational, withdrawn
Description

Valdecoxib was removed from the Canadian, U.S., and E.U. markets in 2005 due to concerns about possible increased risk of heart attack and stroke.

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
BextraNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number181695-72-7
WeightAverage: 314.359
Monoisotopic: 314.072513014
Chemical FormulaC16H14N2O3S
InChI KeyInChIKey=LNPDTQAFDNKSHK-UHFFFAOYSA-N
InChI
InChI=1S/C16H14N2O3S/c1-11-15(12-7-9-14(10-8-12)22(17,19)20)16(18-21-11)13-5-3-2-4-6-13/h2-10H,1H3,(H2,17,19,20)
IUPAC Name
4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)benzene-1-sulfonamide
SMILES
CC1=C(C(=NO1)C1=CC=CC=C1)C1=CC=C(C=C1)S(N)(=O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassStilbenes
SubclassNot Available
Direct parentStilbenes
Alternative parentsBenzenesulfonamides; Sulfonyls; Sulfonamides; Isoxazoles; Polyamines
Substituentsbenzenesulfonamide; benzene; sulfonic acid derivative; sulfonyl; azole; isoxazole; sulfonamide; polyamine; organonitrogen compound
Classification descriptionThis compound belongs to the stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Pharmacology
IndicationFor the treatment of osteoarthritis and dysmenorrhoea
PharmacodynamicsValdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Valdecoxib is used for its anti-inflammatory, analgesic, and antipyretic activities in the management of osteoarthritis (OA) and for the treatment of dysmenorrhea or acute pain. Unlike celecoxib, valdecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism.
Mechanism of actionBoth COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin (PG) H2, the precursor of PGs and thromboxane. Valdecoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, valdecoxib does not inhibit platelet aggregation.
AbsorptionOral bioavailability is 83%.
Volume of distribution
  • 86 L
Protein binding98%
Metabolism

Hepatic (involves CYP3A4 and 2C9)

SubstrateEnzymesProduct
Valdecoxib
Valdecoxib N-glucuronideDetails
Valdecoxib
    Valdecoxib metabolite M2Details
    Valdecoxib metabolite M2
    Valdecoxib metabolite M2 glucuronideDetails
    Valdecoxib metabolite M2
      Valdecoxib metabolite M7Details
      Valdecoxib metabolite M7
        Valdecoxib metabolite M8Details
        Valdecoxib metabolite M2
          Valdecoxib metabolite M5Details
          Valdecoxib metabolite M5
          Valdecoxib metabolite M5 glucuronideDetails
          Valdecoxib
          Valdecoxib metabolite M1Details
          Valdecoxib metabolite M1
          Valdecoxib metabolite M1 glucuronideDetails
          Valdecoxib metabolite M1
            Valdecoxib metabolite M5Details
            Valdecoxib metabolite M1
              Valdecoxib metabolite M4Details
              Valdecoxib metabolite M1
                Valdecoxib metabolite M3Details
                Valdecoxib metabolite M3
                Valdecoxib metabolite M3 glucuronideDetails
                Valdecoxib
                Valdecoxib metabolite M9Details
                Valdecoxib metabolite M9
                Valdecoxib metabolite M3Details
                Valdecoxib metabolite M9
                Valdecoxib metabolite M9 glucuronideDetails
                Route of eliminationValdecoxib is eliminated predominantly via hepatic metabolism with less than 5% of the dose excreted unchanged in the urine and feces. About 70% of the dose is excreted in the urine as metabolites, and about 20% as valdecoxib N-glucuronide.
                Half life8-11 hours
                Clearance
                • oral cl=6 L/h
                • 6 – 7 L/h [In patients undergoing hemodialysis]
                • 6 – 7 L/h [healthy elderly subjects]
                ToxicitySymptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare.
                Affected organisms
                • Humans and other mammals
                PathwaysNot Available
                SNP Mediated EffectsNot Available
                SNP Mediated Adverse Drug ReactionsNot Available
                ADMET
                Predicted ADMET features
                Property Value Probability
                Human Intestinal Absorption + 1.0
                Blood Brain Barrier + 0.9386
                Caco-2 permeable + 0.5
                P-glycoprotein substrate Non-substrate 0.8864
                P-glycoprotein inhibitor I Non-inhibitor 0.8772
                P-glycoprotein inhibitor II Non-inhibitor 0.9157
                Renal organic cation transporter Non-inhibitor 0.8576
                CYP450 2C9 substrate Non-substrate 0.7356
                CYP450 2D6 substrate Substrate 0.8918
                CYP450 3A4 substrate Non-substrate 0.6501
                CYP450 1A2 substrate Non-inhibitor 0.5759
                CYP450 2C9 substrate Inhibitor 0.5385
                CYP450 2D6 substrate Non-inhibitor 0.8875
                CYP450 2C19 substrate Inhibitor 0.5958
                CYP450 3A4 substrate Non-inhibitor 0.8652
                CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7649
                Ames test Non AMES toxic 0.8277
                Carcinogenicity Non-carcinogens 0.7399
                Biodegradation Not ready biodegradable 0.9948
                Rat acute toxicity 2.0680 LD50, mol/kg Not applicable
                hERG inhibition (predictor I) Weak inhibitor 0.9708
                hERG inhibition (predictor II) Non-inhibitor 0.8652
                Pharmacoeconomics
                Manufacturers
                • Gd searle llc
                Packagers
                Dosage forms
                FormRouteStrength
                TabletOral
                PricesNot Available
                Patents
                CountryPatent NumberApprovedExpires (estimated)
                United States71354891997-08-122017-08-12
                United States56332721995-02-132015-02-13
                Canada22128362003-08-122016-02-12
                Properties
                Statesolid
                Experimental Properties
                PropertyValueSource
                logP3.2Not Available
                Predicted Properties
                PropertyValueSource
                water solubility3.48e-02 g/lALOGPS
                logP3.32ALOGPS
                logP2.82ChemAxon
                logS-4ALOGPS
                pKa (strongest acidic)10.06ChemAxon
                pKa (strongest basic)0.42ChemAxon
                physiological charge0ChemAxon
                hydrogen acceptor count3ChemAxon
                hydrogen donor count1ChemAxon
                polar surface area86.19ChemAxon
                rotatable bond count3ChemAxon
                refractivity84.71ChemAxon
                polarizability31.76ChemAxon
                number of rings3ChemAxon
                bioavailability1ChemAxon
                rule of fiveYesChemAxon
                Ghose filterYesChemAxon
                Veber's ruleNoChemAxon
                MDDR-like ruleNoChemAxon
                Spectra
                SpectraNot Available
                References
                Synthesis Reference

                Eswaraiah Sajja, Anumula Reddy, Aalla Sampath, Gilla Goverdhan, “Process for preparing crystalline form A of valdecoxib.” U.S. Patent US20050272787, issued December 08, 2005.

                US20050272787
                General ReferenceNot Available
                External Links
                ResourceLink
                PubChem Compound119607
                PubChem Substance46506229
                ChemSpider106796
                BindingDB13063
                Therapeutic Targets DatabaseDAP001541
                PharmGKBPA10226
                HETCOX
                Drug Product Database2246622
                RxListhttp://www.rxlist.com/cgi/generic/bextra.htm
                Drugs.comhttp://www.drugs.com/mtm/valdecoxib.html
                WikipediaValdecoxib
                ATC CodesM01AH03
                AHFS CodesNot Available
                PDB EntriesNot Available
                FDA labelshow(82.8 KB)
                MSDSshow(70.6 KB)
                Interactions
                Drug Interactions
                Drug
                FluconazoleFluconazole may increase the effect and toxicity of valdecoxib.
                KetoconazoleKetoconazole may increase the effect and toxicity of valdecoxib.
                LithiumThe COX-2 inhibitor increases serum levels of lithium
                Food InteractionsNot Available

                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. Talley JJ, Brown DL, Carter JS, Graneto MJ, Koboldt CM, Masferrer JL, Perkins WE, Rogers RS, Shaffer AF, Zhang YY, Zweifel BS, Seibert K: 4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, valdecoxib: a potent and selective inhibitor of COX-2. J Med Chem. 2000 Mar 9;43(5):775-7. Pubmed
                2. Jain KK: Evaluation of intravenous parecoxib for the relief of acute post-surgical pain. Expert Opin Investig Drugs. 2000 Nov;9(11):2717-23. Pubmed
                3. Yuan JJ, Yang DC, Zhang JY, Bible R Jr, Karim A, Findlay JW: Disposition of a specific cyclooxygenase-2 inhibitor, valdecoxib, in human. Drug Metab Dispos. 2002 Sep;30(9):1013-21. Pubmed
                4. Tacconelli S, Capone ML, Sciulli MG, Ricciotti E, Patrignani P: The biochemical selectivity of novel COX-2 inhibitors in whole blood assays of COX-isozyme activity. Curr Med Res Opin. 2002;18(8):503-11. Pubmed
                5. Hood WF, Gierse JK, Isakson PC, Kiefer JR, Kurumbail RG, Seibert K, Monahan JB: Characterization of celecoxib and valdecoxib binding to cyclooxygenase. Mol Pharmacol. 2003 Apr;63(4):870-7. Pubmed
                6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
                7. Gierse JK, Zhang Y, Hood WF, Walker MC, Trigg JS, Maziasz TJ, Koboldt CM, Muhammad JL, Zweifel BS, Masferrer JL, Isakson PC, Seibert K: Valdecoxib: assessment of cyclooxygenase-2 potency and selectivity. J Pharmacol Exp Ther. 2005 Mar;312(3):1206-12. Epub 2004 Oct 19. Pubmed

                1. 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

                2. 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

                3. 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

                4. UDP-glucuronosyltransferase 1-9

                Kind: protein

                Organism: Human

                Pharmacological action: unknown

                Actions: substrate

                Components

                Name UniProt ID Details
                UDP-glucuronosyltransferase 1-9 O60656 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

                5. Cytochrome P450 2C19

                Kind: protein

                Organism: Human

                Pharmacological action: unknown

                Actions: inhibitor

                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

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