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Identification
Name Oxaprozin
Accession Number DB00991 (APRD00030)
Type small molecule
Groups approved
Description

Oxaprozin is a non-narcotic, non-steroidal anti-inflammatory drug (NSAID), used to relieve the inflammation, swelling, stiffness, and joint pain associated with osteoarthritis and rheumatoid arthritis.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Oxaprozina [INN-Spanish]
  • Oxaprozine [INN-French]
  • Oxaprozinum [INN-Latin]
Brand names
  • Alvo
  • Daypro
  • Daypro Alta
  • Deflam
  • Voir
Brand name mixtures Not Available
Categories
  • Anti-inflammatory Agents
  • Nonsteroidal Anti-inflammatory Agents (NSAIAs)
CAS number 21256-18-8
Weight Average: 293.3166
Monoisotopic: 293.105193351
Chemical Formula C18H15NO3
InChI Key InChIKey=OFPXSFXSNFPTHF-UHFFFAOYSA-N
InChI
InChI=1S/C18H15NO3/c20-16(21)12-11-15-19-17(13-7-3-1-4-8-13)18(22-15)14-9-5-2-6-10-14/h1-10H,11-12H2,(H,20,21)
Plain Text
IUPAC Name
3-(diphenyl-1,3-oxazol-2-yl)propanoic acid
SMILES
OC(=O)CCC1=NC(=C(O1)C1=CC=CC=C1)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpropenes
Substructures
  • Hydroxy Compounds
  • Acetates
  • Phenylpropenes
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Oxazoles
  • Imines
Pharmacology
Indication Used to relieve the inflammation, swelling, stiffness, and joint pain associated with rheumatoid arthritis and osteoarthritis.
Pharmacodynamics Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Oxaprozin is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and to alleviate moderate pain.
Mechanism of action Anti-inflammatory effects of Oxaprozin are believed to be due to inhibition of cylooxygenase in platelets which leads to the blockage of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Oxaprozin is a non-selective NSAID, with a cell assay system showing lower COX-2 selectivity implying higher COX-1 selectivity.
Absorption Oxaprozin is 95% absorbed after oral administration. Food may reduce the rate of absorption of oxaprozin, but the extent of absorption is unchanged. Antacids do not significantly affect the extent and rate of oxaprozin absorption.
Volume of distribution
  • 11 to 17 L/70 kg
Protein binding >99.5% bound to albumin
Metabolism

Hepatic. Ester and ether glucuronide are the major conjugated metabolites of oxaprozin, and do not have significant pharmacologic activity.
Route of elimination Oxaprozin is expected to be excreted in human milk based on its physical-chemical properties; however, the amount of oxaprozin excreted in breast milk has not been evaluated. Approximately 95% of oxaprozin is metabolized by the liver. Approximately 5% of the oxaprozin dose is excreted unchanged in the urine. Sixty-five percent (65%) of the dose is excreted in the urine and 35% in the feces as metabolite. Biliary excretion of unchanged oxaprozin is a minor pathway. Several oxaprozin metabolites have been identified in human urine or feces.
Half life 54.9 hours
Clearance Not Available
Toxicity Oral, mouse: LD50 = 1210 mg/kg; Oral, rabbit: LD50 = 172 mg/kg; Oral, rat: LD50 = 4470 mg/kg
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00113 Oxaprozin Pathway SMP00113
Pharmacoeconomics
Manufacturers
  • Gd searle llc
  • Actavis elizabeth llc
  • Apotex inc etobicoke site
  • Caraco pharmaceutical laboratories ltd
  • Dr reddys laboratories ltd
  • Genpharm inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Daypro 600 mg tablet 2.98 USD tablet
Daypro 600 mg caplet 2.87 USD caplet
Oxaprozin 600 mg tablet 1.54 USD tablet
Patents
Country Patent Number Approved Expires
United States 6030643 1997-05-16 2017-05-16
Properties
State solid
Melting point 158 - 159 oC
Experimental Properties
Property Value Source
water solubility Insoluble PhysProp
logP 3.7 PhysProp
pKa 4.3 Various sources
Predicted Properties
Property Value Source
water solubility 3.25e-02 g/l ALOGPS
logP 3.33 ALOGPS
logP 3.46 ChemAxon Molconvert
logS -3.96 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 63.33 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 81.88 ChemAxon Molconvert
polarizability 31.69 ChemAxon Molconvert
References
Synthesis Reference
  1. Zhou XP, Zhang MX, Sun W, Yang XH, Wang GS, Sui DY, Yu XF, Qu SC: Design, synthesis, and in-vivo evaluation of 4,5-diaryloxazole as novel nonsteroidal anti-inflammatory drug. Biol Pharm Bull. 2009 Dec;32(12):1986-90. Pubmed
General Reference
  1. Heller B, Tarricone R: Oxaprozin versus diclofenac in NSAID-refractory periarthritis pain of the shoulder. Curr Med Res Opin. 2004 Aug;20(8):1279-90. Pubmed
External Links
Resource Link
KEGG Drug D00463 Link_out
KEGG Compound C07356 Link_out
PubChem Compound 4614 Link_out
PubChem Substance 46506429 Link_out
ChemSpider 4453 Link_out
BindingDB 50002861 Link_out
Therapeutic Targets Database DAP000622 Link_out
PharmGKB PA450730 Link_out
Drug Product Database 2243661 Link_out
RxList http://www.rxlist.com/cgi/generic/oxaproz.htm Link_out
Drugs.com http://www.drugs.com/cdi/oxaprozin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Oxaprozin Link_out
ATC Codes
  • M01AE12
AHFS Codes
  • 28:08.04.92
PDB Entries Not Available
FDA label show (47 KB)
MSDS show (63.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food, usually once a day after breakfast. Food decreases the rate of absorption but not the amount absorbed. Avoid alcohol.
Targets

1. Prostaglandin G/H synthase 1

Pharmacological action: yes
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. Kawai S: Cyclooxygenase selectivity and the risk of gastro-intestinal complications of various non-steroidal anti-inflammatory drugs: a clinical consideration. Inflamm Res. 1998 Oct;47 Suppl 2:S102-6. Pubmed
  2. Kean WF: Oxaprozin: kinetic and dynamic profile in the treatment of pain. Curr Med Res Opin. 2004 Aug;20(8):1275-7. Pubmed
  3. Zhou XP, Zhang MX, Sun W, Yang XH, Wang GS, Sui DY, Yu XF, Qu SC: Design, synthesis, and in-vivo evaluation of 4,5-diaryloxazole as novel nonsteroidal anti-inflammatory drug. Biol Pharm Bull. 2009 Dec;32(12):1986-90. Pubmed
  4. Ottonello L, Bertolotto M, Montecucco F, Bianchi G, Dallegri F: Delayed apoptosis of human monocytes exposed to immune complexes is reversed by oxaprozin: role of the Akt/IkappaB kinase/nuclear factor kappaB pathway. Br J Pharmacol. 2009 May;157(2):294-306. Epub 2009 Mar 26. Pubmed
  5. Yood MU, Watkins E, Wells K, Kucera G, Johnson CC: The impact of NSAID or COX-2 inhibitor use on the initiation of antihypertensive therapy. Pharmacoepidemiol Drug Saf. 2006 Dec;15(12):852-60. Pubmed

2. 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. Yood MU, Watkins E, Wells K, Kucera G, Johnson CC: The impact of NSAID or COX-2 inhibitor use on the initiation of antihypertensive therapy. Pharmacoepidemiol Drug Saf. 2006 Dec;15(12):852-60. Pubmed
  2. Kawai S, Nishida S, Kato M, Furumaya Y, Okamoto R, Koshino T, Mizushima Y: Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells. Eur J Pharmacol. 1998 Apr 17;347(1):87-94. Pubmed
  3. Kawai S: Cyclooxygenase selectivity and the risk of gastro-intestinal complications of various non-steroidal anti-inflammatory drugs: a clinical consideration. Inflamm Res. 1998 Oct;47 Suppl 2:S102-6. Pubmed
  4. Yamazaki R, Kusunoki N, Matsuzaki T, Hashimoto S, Kawai S: Nonsteroidal anti-inflammatory drugs induce apoptosis in association with activation of peroxisome proliferator-activated receptor gamma in rheumatoid synovial cells. J Pharmacol Exp Ther. 2002 Jul;302(1):18-25. Pubmed
  5. Zhou XP, Zhang MX, Sun W, Yang XH, Wang GS, Sui DY, Yu XF, Qu SC: Design, synthesis, and in-vivo evaluation of 4,5-diaryloxazole as novel nonsteroidal anti-inflammatory drug. Biol Pharm Bull. 2009 Dec;32(12):1986-90. Pubmed
  6. Ottonello L, Bertolotto M, Montecucco F, Bianchi G, Dallegri F: Delayed apoptosis of human monocytes exposed to immune complexes is reversed by oxaprozin: role of the Akt/IkappaB kinase/nuclear factor kappaB pathway. Br J Pharmacol. 2009 May;157(2):294-306. Epub 2009 Mar 26. Pubmed
Enzymes

1. 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. 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 January 04, 2011 15:13

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.