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Identification
Name Piroxicam
Accession Number DB00554 (APRD01187)
Type small molecule
Groups approved
Description

A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • AK1015
  • piroxicam
Brand names
  • Akten
  • Apo-Piroxicam
  • Artroxicam
  • Baxo
  • Bruxicam
  • Caliment
  • Erazon
  • Feldene
  • Flogobene
  • Geldene
  • Improntal
  • Larapam
  • Pipoxicam
  • Pirkam
  • Piroflex
  • piroxicam usp
  • Reudene
  • Riacen
  • Roxicam
  • Roxiden
  • Sasulen
  • Solocalm
  • Zunden
Brand name mixtures Not Available
Categories
  • Cyclooxygenase Inhibitors
CAS number 36322-90-4
Weight Average: 331.346
Monoisotopic: 331.062676609
Chemical Formula C15H13N3O4S
InChI Key InChIKey=LDJVNWFKNMYYNT-FYWRMAATSA-N
InChI
InChI=1S/C15H13N3O4S/c1-18-13(15(20)17-12-8-4-5-9-16-12)14(19)10-6-2-3-7-11(10)23(18,21)22/h2-9,20H,1H3,(H,16,17)/b15-13+
Plain Text
IUPAC Name
(3E)-3-{hydroxy[(pyridin-2-yl)amino]methylidene}-2-methyl-3,4-dihydro-2H-1$l^{6},2-benzothiazine-1,1,4-trione
SMILES
CN1\C(C(=O)C2=C(C=CC=C2)S1(=O)=O)=C(\O)NC1=NC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzenesulfonamides
  • Phenethylamines
Substructures
  • Hydroxy Compounds
  • Amino Ketones
  • Pyridines and Derivatives
  • Sulfonyls
  • Benzene and Derivatives
  • Benzenesulfonamides
  • Aminopyridines and Derivatives
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Sulfonamides
  • Benzoyl Derivatives
  • Ketones
Pharmacology
Indication For treatment of osteoarthritis and rheumatoid arthritis.
Pharmacodynamics Piroxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Piroxicam works by reducing hormones that cause inflammation and pain in the body. Piroxicam is used to reduce the pain, inflammation, and stiffness caused by rheumatoid arthritis and osteoarthritis.
Mechanism of action The antiinflammatory effect of Piroxicam may result from the reversible inhibition of cyclooxygenase, causing the peripheral inhibition of prostaglandin synthesis. The prostaglandins are produced by an enzyme called Cox-1. Piroxicam blocks the Cox-1 enzyme, resulting into the disruption of production of prostaglandins. Piroxicam also inhibits the migration of leukocytes into sites of inflammation and prevents the formation of thromboxane A2, an aggregating agent, by the platelets.
Absorption Well absorbed following oral administration.
Volume of distribution
  • 0.14 L/kg
Protein binding Not Available
Metabolism

Renal

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2C9 5'-Hydroxypiroxicam 5'-hydroxylation 40 0
Route of elimination Piroxicam and its biotransformation products are excreted in urine and feces, with about twice as much appearing in the urine as in the feces. Approximately 5% of a piroxicam dose is excreted unchanged. However, a substantial portion of piroxicam elimination occurs by hepatic metabolism. Piroxicam is excreted into human milk.
Half life 30 to 86 hours
Clearance Not Available
Toxicity Symptoms of overdose include drowsiness, nausea, stomach pain, and/or vomiting.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00077 Piroxicam Pathway SMP00077
Pharmacoeconomics
Manufacturers
  • Akorn inc
  • Pfizer laboratories div pfizer inc
  • Egis pharmaceuticals
  • Genpharm pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Nostrum laboratories inc
  • Roxane laboratories inc
  • Scs pharmaceuticals
  • Teva pharmaceuticals usa inc
  • Teva pharmaceuticals usa
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Suppository Rectal
Tablet Oral
Prices
Unit description Cost Unit
Piroxicam powder 13.16 USD g
Akten 3.5% drops 7.5 USD ml
Feldene 20 mg capsule 4.93 USD capsule
Feldene 10 mg capsule 2.82 USD capsule
Piroxicam 20 mg capsule 2.69 USD capsule
Pms-Piroxicam 20 mg Suppository 1.82 USD suppository
Piroxicam 10 mg capsule 1.44 USD capsule
Apo-Piroxicam 20 mg Capsule 0.75 USD capsule
Novo-Pirocam 20 mg Capsule 0.75 USD capsule
Nu-Pirox 20 mg Capsule 0.75 USD capsule
Apo-Piroxicam 10 mg Capsule 0.43 USD capsule
Gen-Piroxicam 10 mg Capsule 0.43 USD capsule
Novo-Pirocam 10 mg Capsule 0.43 USD capsule
Nu-Pirox 10 mg Capsule 0.43 USD capsule
Patents Not Available
Properties
State solid
Melting point 198-200 oC
Experimental Properties
Property Value Source
water solubility 23 mg/L PhysProp
logP 3 PhysProp
logS -4.16 [ADME Research, USCD] PhysProp
Caco2 permeability -4.45 [ADME Research, USCD] BiGG
pKa 6.3 Various sources
Predicted Properties
Property Value Source
water solubility 6.05e-02 g/l ALOGPS
logP 1.81 ALOGPS
logP 1.31 ChemAxon Molconvert
logS -3.74 ALOGPS
pKa 13.92 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 99.60 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 96.17 ChemAxon Molconvert
polarizability 31.56 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00127 Link_out
KEGG Compound C01608 Link_out
PubChem Compound 5280452 Link_out
PubChem Substance 46505225 Link_out
ChemSpider 4444107 Link_out
ChEBI 8249 Link_out
ChEMBL 8249 Link_out
Therapeutic Targets Database DAP000181 Link_out
PharmGKB PA450985 Link_out
Drug Product Database 658839 Link_out
RxList http://www.rxlist.com/cgi/generic/piroxicam.htm Link_out
Drugs.com http://www.drugs.com/cdi/piroxicam.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/fel1173.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Piroxicam Link_out
ATC Codes
  • M01AC01
  • M02AA07
  • S01BC06
AHFS Codes
  • 28:08.04.92
PDB Entries Not Available
FDA label show (74.3 KB)
MSDS show (73.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food. Avoid alcohol.
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. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73. Pubmed
  2. Bugajski J, Glod R, Gadek-Michalska A, Bugajski AJ: Involvement of constitutive (COX-1) and inducible cyclooxygenase (COX-2) in the adrenergic-induced ACTH and corticosterone secretion. J Physiol Pharmacol. 2001 Dec;52(4 Pt 2):795-809. Pubmed
  3. Fackovcova D, Kristova V, Kriska M: Renal damage induced by the treatment with non-opioid analgesics—theoretical assumption or clinical significance. Bratisl Lek Listy. 2000;101(8):417-22. Pubmed
  4. Raju J, Bird RP: Differential modulation of transforming growth factor-betas and cyclooxygenases in the platelet lysates of male F344 rats by dietary lipids and piroxicam. Mol Cell Biochem. 2002 Feb;231(1-2):139-46. Pubmed
  5. Veiga AP, Duarte ID, Avila MN, da Motta PG, Tatsuo MA, Francischi JN: Prevention by celecoxib of secondary hyperalgesia induced by formalin in rats. Life Sci. 2004 Oct 22;75(23):2807-17. 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

Pharmacological action: unknown
Actions: inhibitor

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

Organism class: human
UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73. Pubmed
  2. Bugajski J, Glod R, Gadek-Michalska A, Bugajski AJ: Involvement of constitutive (COX-1) and inducible cyclooxygenase (COX-2) in the adrenergic-induced ACTH and corticosterone secretion. J Physiol Pharmacol. 2001 Dec;52(4 Pt 2):795-809. Pubmed
  3. Fackovcova D, Kristova V, Kriska M: Renal damage induced by the treatment with non-opioid analgesics—theoretical assumption or clinical significance. Bratisl Lek Listy. 2000;101(8):417-22. Pubmed
  4. Raju J, Bird RP: Differential modulation of transforming growth factor-betas and cyclooxygenases in the platelet lysates of male F344 rats by dietary lipids and piroxicam. Mol Cell Biochem. 2002 Feb;231(1-2):139-46. Pubmed
  5. Veiga AP, Duarte ID, Avila MN, da Motta PG, Tatsuo MA, Francischi JN: Prevention by celecoxib of secondary hyperalgesia induced by formalin in rats. Life Sci. 2004 Oct 22;75(23):2807-17. Pubmed
Enzymes

1. Cytochrome P450 2C9

Actions: substrate, inhibitor

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. 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. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Pelkonen O, Maenpaa J, Taavitsainen P, Rautio A, Raunio H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica. 1998 Dec;28(12):1203-53. Pubmed
  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

2. Cytochrome P450 2C8

Actions: substrate, inhibitor

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. 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. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. Pubmed
  3. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  4. 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. Tsuda M, Sekine T, Takeda M, Cha SH, Kanai Y, Kimura M, Endou H: Transport of ochratoxin A by renal multispecific organic anion transporter 1. J Pharmacol Exp Ther. 1999 Jun;289(3):1301-5. Pubmed

2. Solute carrier family 22 member 8

Actions: inhibitor

Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. Pubmed
  2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  3. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed

3. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out
Gene: SLC22A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H: Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta. 2002 Jun 12;1590(1-3):64-75. Pubmed
  2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
Carriers

1. Serum albumin

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 colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bertucci C, Wainer IW: Improved chromatographic performance of a modified human albumin based stationary phase. Chirality. 1997;9(4):335-40. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on October 20, 2011 16:51

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.