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Identification
Name Celecoxib
Accession Number DB00482 (APRD00373)
Type small molecule
Groups approved
Description

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. It is marketed by Pfizer under the brand name Celebrex. In some countries, it is branded Celebra. Celecoxib is available by prescription in capsule form.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Celocoxib
Salts Not Available
Brand names
Name Company
Celebra
Celebrex
Brand mixtures Not Available
Categories
  • Cyclooxygenase Inhibitors
CAS number 169590-42-5
Weight Average: 381.372
Monoisotopic: 381.075882012
Chemical Formula C17H14F3N3O2S
InChI Key InChIKey=RZEKVGVHFLEQIL-UHFFFAOYSA-N
InChI
InChI=1S/C17H14F3N3O2S/c1-11-2-4-12(5-3-11)15-10-16(17(18,19)20)22-23(15)13-6-8-14(9-7-13)26(21,24)25/h2-10H,1H3,(H2,21,24,25)
Plain Text
IUPAC Name
4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamide
SMILES
CC1=CC=C(C=C1)C1=CC(=NN1C1=CC=C(C=C1)S(N)(=O)=O)C(F)(F)F
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Benzenesulfonamides
  • Sulfanilamides
Substructures
  • Pyrazoles
  • Sulfonyls
  • Halogen Derivatives
  • Benzene and Derivatives
  • Benzenesulfonamides
  • Heterocyclic compounds
  • Aromatic compounds
  • Sulfanilamides
  • Sulfonamides
  • Imines
  • Anilines
Pharmacology
Indication For relief and management of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, acute pain, primary dysmenorrhea and oral adjunct to usual care for patients with familial adenomatous polyposis
Pharmacodynamics Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Celecoxib is used to treat rheumatoid arthritis, osteoarthritis, and familial adenomatous polyposis (FAP). Because of its lack of platelet effects, celecoxib is not a substitute for aspirin for cardiovascular prophylaxis. It is not known if there are any effects of celecoxib on platelets that may contribute to the increased risk of serious cardiovascular thrombotic adverse events associated with the use of celecoxib. Inhibition of PGE2 synthesis may lead to sodium and water retention through increased reabsorption in the renal medullary thick ascending loop of Henle and perhaps other segments of the distal nephron. In the collecting ducts, PGE2 appears to inhibit water reabsorption by counteracting the action of antidiuretic hormone.
Mechanism of action The mechanism of action of celecoxib is believed to be due to inhibition of prostaglandin synthesis. Unlike most NSAIDs, which inhibit both types of cyclooxygenases (COX-1 and COX-2), celecoxib is a selective noncompetitive inhibitor of cyclooxygenase-2 (COX-2) enzyme. It binds with its polar sulfonamide side chain to a hydrophilic side pocket region close to the active COX-2 binding site. Both COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin (PG) H2, the precursor of PGs and thromboxane.
Absorption Well absorbed in the gastrointestinal tract. When taken with a high fat meal, peak plasma levels are delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%.
Volume of distribution
  • 400 L
Protein binding 97%, primarily to albumin and, to a lesser extent, a1-acid glycoprotein.
Metabolism Hepatic. Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been identified in human plasma. These metabolites are inactive as COX-1 or COX-2 inhibitors.
Route of elimination Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug recovered in the urine and feces.
Half life Approximately 11 hours.
Clearance
  • 500 mL/min
Toxicity Symptoms of overdose include breathing difficulties, coma, drowsiness, gastrointestinal bleeding, high blood pressure, kidney failure, nausea, sluggishness, stomach pain, and vomiting.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00096 Celecoxib Pathway SMP00096
Pharmacoeconomics
Manufacturers
  • Gd searle llc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Celebrex 400 mg capsule 6.78 USD capsule
Celebrex 200 mg capsule 4.52 USD capsule
Celebrex 100 mg capsule 2.75 USD capsule
Celebrex 50 mg capsule 1.26 USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 5972986 1998-04-14 2018-04-14
United States 5466823 1993-11-30 2013-11-30
Canada 2267186 2002-05-14 2017-10-14
Canada 2177576 1999-10-26 2014-11-14
Properties
State solid
Experimental Properties
Property Value Source
melting point 158 °C PhysProp
water solubility Very low water solubility (3.3 mg/L) Not Available
logP 3.9 Not Available
Predicted Properties
Property Value Source
water solubility 5.03e-03 g/l ALOGPS
logP 3.99 ALOGPS
logP 4.01 ChemAxon
logS -4.9 ALOGPS
pKa (strongest acidic) 10.7 ChemAxon
pKa (strongest basic) -0.42 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 77.98 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 92.23 ChemAxon
polarizability 35.2 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Malhotra S, Shafiq N, Pandhi P: COX-2 inhibitors: a CLASS act or Just VIGORously promoted. MedGenMed. 2004 Mar 23;6(1):6. Pubmed
  2. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS: Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA. 2000 Sep 13;284(10):1247-55. Pubmed
  3. Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005 Mar 17;352(11):1071-80. Epub 2005 Feb 15. Pubmed
  4. Yelland MJ, Nikles CJ, McNairn N, Del Mar CB, Schluter PJ, Brown RM: Celecoxib compared with sustained-release paracetamol for osteoarthritis: a series of n-of-1 trials. Rheumatology (Oxford). 2007 Jan;46(1):135-40. Epub 2006 Jun 15. Pubmed
  5. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET: Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006 Aug 31;355(9):873-84. Pubmed
External Links
Resource Link
KEGG Drug D00567 Link_out
KEGG Compound C07589 Link_out
PubChem Compound 2662 Link_out
PubChem Substance 46505596 Link_out
ChemSpider 2562 Link_out
BindingDB 11639 Link_out
ChEBI 3520 Link_out
ChEMBL 3520 Link_out
Therapeutic Targets Database DAP000737 Link_out
PharmGKB PA448871 Link_out
HET CEL Link_out
Drug Product Database 2239941 Link_out
RxList http://www.rxlist.com/cgi/generic/coxib.htm Link_out
Drugs.com http://www.drugs.com/celecoxib.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Celecoxib Link_out
ATC Codes
  • L01XX33
  • M01AH01
AHFS Codes
  • 28:08.04.08
PDB Entries Not Available
FDA label show (174 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol Celecoxib may increase the anticoagulant effect of acenocoumarol.
Anisindione Celecoxib may increase the anticoagulant effect of anisindione.
Azilsartan medoxomil Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Colesevelam Bile 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.
Dicumarol Celecoxib may increase the anticoagulant effect of dicumarol.
Eltrombopag Eltrombopag increases levels of Celecoxib via metabolism decrease.
Fluconazole Fluconazole may increase the effect of celecoxib.
Lithium The COX-2 inhibitor increases serum levels of lithium
Pralatrexate NSAIDs 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.
Rifampin Rifampin, a strong CYP2C9 inducer, may decrease the serum levels of celecoxib by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects if rifampin is initiated, discontinued or dose changed.
Telmisartan Concomitant use of Telmisartan and Celecoxib may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Timolol The NSAID, Celecoxib, may antagonize the antihypertensive effect of Timolol.
Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Celecoxib. Consider alternate therapy or monitor for changes in Celecobix therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Trandolapril The NSAID, Celecoxib, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Celecoxib is initiated, discontinued or dose changed.
Treprostinil The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Celecoxib. Monitor for increased bleeding during concomitant thearpy.
Tretinoin The moderate CYP2C8 inhibitor, Celecoxib, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Celecoxib is initiated, discontinued to dose changed.
Vilazodone Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). To minimize the risk of bleeding associated with this combination, consider using alternative analgesics, when appropriate, and/or addition of an gastroprotective agent, such as a proton pump inhibitor for the time that combined selective serotonin reuptake inhibitor (SSRIs) and nonsteroidal anti-inflammatory drugs (NSAIDs) is necessary.
Warfarin Celecoxib may increase the anticoagulant effect of warfarin.
Food Interactions
  • Take without regard to meals.
  • Taking this product with a high-fat meal will delay the Cmax, but total absorption will be increased by 10 to 20%.
Targets

1. Prostaglandin G/H synthase 2

Pharmacological action: yes
Actions: inhibitor

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

Organism class: human
UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sigthorsson G, Simpson RJ, Walley M, Anthony A, Foster R, Hotz-Behoftsitz C, Palizban A, Pombo J, Watts J, Morham SG, Bjarnason I: COX-1 and 2, intestinal integrity, and pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in mice. Gastroenterology. 2002 Jun;122(7):1913-23. Pubmed
  2. Scheiman JM: Outcomes studies of the gastrointestinal safety of cyclooxygenase-2 inhibitors. Cleve Clin J Med. 2002;69 Suppl 1:SI40-6. Pubmed
  3. Reddy BS, Rao CV: Novel approaches for colon cancer prevention by cyclooxygenase-2 inhibitors. J Environ Pathol Toxicol Oncol. 2002;21(2):155-64. Pubmed
  4. Ahmad SR, Kortepeter C, Brinker A, Chen M, Beitz J: Renal failure associated with the use of celecoxib and rofecoxib. Drug Saf. 2002;25(7):537-44. Pubmed
  5. Lu S, Zhang X, Badawi AF, El-Sohemy A, Archer MC: Cyclooxygenase-2 inhibitor celecoxib inhibits promotion of mammary tumorigenesis in rats fed a high fat diet rich in n-6 polyunsaturated fatty acids. Cancer Lett. 2002 Oct 8;184(1):7-12. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. 3-phosphoinositide-dependent protein kinase 1

Pharmacological action: unknown
Actions: inhibitor

Phosphorylates and activates not only PKB/AKT, but also PKA, PKC-zeta, RPS6KA1 and RPS6KB1. May play a general role in signaling processes and in development. Isoform 3 is catalytically inactive

Organism class: human
UniProt ID: O15530 Link_out
Gene: PDPK1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kulp SK, Yang YT, Hung CC, Chen KF, Lai JP, Tseng PH, Fowble JW, Ward PJ, Chen CS: 3-phosphoinositide-dependent protein kinase-1/Akt signaling represents a major cyclooxygenase-2-independent target for celecoxib in prostate cancer cells. Cancer Res. 2004 Feb 15;64(4):1444-51. Pubmed
  2. Zhu J, Huang JW, Tseng PH, Yang YT, Fowble J, Shiau CW, Shaw YJ, Kulp SK, Chen CS: From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res. 2004 Jun 15;64(12):4309-18. Pubmed
  3. Tong Z, Wu X, Ovcharenko D, Zhu J, Chen CS, Kehrer JP: Neutrophil gelatinase-associated lipocalin as a survival factor. Biochem J. 2005 Oct 15;391(Pt 2):441-8. Pubmed
  4. Li J, Zhu J, Melvin WS, Bekaii-Saab TS, Chen CS, Muscarella P: A structurally optimized celecoxib derivative inhibits human pancreatic cancer cell growth. J Gastrointest Surg. 2006 Feb;10(2):207-14. Pubmed
  5. Tseng PH, Wang YC, Weng SC, Weng JR, Chen CS, Brueggemeier RW, Shapiro CL, Chen CY, Dunn SE, Pollak M, Chen CS: Overcoming trastuzumab resistance in HER2-overexpressing breast cancer cells by using a novel celecoxib-derived phosphoinositide-dependent kinase-1 inhibitor. Mol Pharmacol. 2006 Nov;70(5):1534-41. Epub 2006 Aug 3. Pubmed
Enzymes

1. Cytochrome P450 2C8

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Rodrigues AD: Impact of CYP2C9 genotype on pharmacokinetics: are all cyclooxygenase inhibitors the same? Drug Metab Dispos. 2005 Nov;33(11):1567-75. Epub 2005 Aug 23. Pubmed
  2. Martinez C, Blanco G, Garcia-Martin E, Agundez JA: [Clinical pharmacogenomics for CYP2C8 and CYP2C9: general concepts and application to the use of NSAIDs]. Farm Hosp. 2006 Jul-Aug;30(4):240-8. Pubmed

2. Cytochrome P450 2C9

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Davies NM, McLachlan AJ, Day RO, Williams KM: Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet. 2000 Mar;38(3):225-42. 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. 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
  4. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  5. 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
  6. Lin Y, Lu P, Tang C, Mei Q, Sandig G, Rodrigues AD, Rushmore TH, Shou M: Substrate inhibition kinetics for cytochrome P450-catalyzed reactions. Drug Metab Dispos. 2001 Apr;29(4 Pt 1):368-74. Pubmed

3. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Werner U, Werner D, Rau T, Fromm MF, Hinz B, Brune K: Celecoxib inhibits metabolism of cytochrome P450 2D6 substrate metoprolol in humans. Clin Pharmacol Ther. 2003 Aug;74(2):130-7. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Multidrug resistance-associated protein 4

Actions: inhibitor

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19