Identification

Name
Etoricoxib
Accession Number
DB01628
Description

Etoricoxib is a new COX-2 selective inhibitor. Current therapeutic indications are: treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout. Like any other COX-2 selective inhibitor, Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2) to reduce the generation of prostaglandins (PGs) from arachidonic acid. It is approved in more than 60 countries worldwide but not in the US.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 358.842
Monoisotopic: 358.054276131
Chemical Formula
C18H15ClN2O2S
Synonyms
  • 5-chloro-2-(6-methylpyridin-3-yl)-3-(4-(methylsulfonyl)phenyl)pyridine
  • 5-Chloro-3-(4-methanesulfonyl-phenyl)-6'-methyl-[2,3']bipyridinyl
  • 5-chloro-6'-methyl-3-(p-(methylsulfonyl)phenyl)-2,3'-bipyridine
  • Etoricoxib
  • étoricoxib
  • Etoricoxibum
External IDs
  • L-791456
  • L791456
  • MK-0663
  • MK-663

Pharmacology

Indication

For the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout.

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Etoricoxib is a COX-2 selective inhibitor (approximately 106 times more selective for COX-2 inhibition over COX-1).

Mechanism of action

Like any other COX-2 selective inhibitor Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2), preventing production of prostaglandins (PGs) from arachidonic acid.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Humans
Absorption

Bioavailability is 100% following oral administration.

Volume of distribution
Not Available
Protein binding

92%

Metabolism

Hepatic, primarily via CYP3A4.

Hover over products below to view reaction partners

Route of elimination
Not Available
Half-life

22 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

This reduced activity is the cause of reduced gastrointestinal toxicity, as demonstrated in several large clinical trials performed with different COXIB (see below links on NEJM and The Lancet). Some clinical trials and meta-analysis showed that treatment with COXIB lead to increased incidence of cardiovascular adverse events compared to placebo

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Etoricoxib Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirEtoricoxib may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Etoricoxib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Etoricoxib can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Etoricoxib is combined with Abciximab.
AbirateroneThe serum concentration of Etoricoxib can be increased when it is combined with Abiraterone.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Etoricoxib.
AcarboseEtoricoxib may decrease the excretion rate of Acarbose which could result in a higher serum level.
AcebutololEtoricoxib may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Etoricoxib is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Etoricoxib is combined with Acemetacin.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

Product Ingredients
IngredientUNIICASInChI Key
Etoricoxib hydrochloride138Y28RY5E202409-40-3NNGHGPAKTWAHHB-UHFFFAOYSA-N
International/Other Brands
Algix / Arcoxia / Coxyveen (Solmarc Lifesciences) / Etorix / Nucoxia / Tauxib

Categories

ATC Codes
M01AH05 — Etoricoxib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as bipyridines and oligopyridines. These are organic compounds containing two pyridine rings linked to each other.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Bipyridines and oligopyridines
Direct Parent
Bipyridines and oligopyridines
Alternative Parents
Phenylpyridines / Benzenesulfonyl compounds / Methylpyridines / Aryl chlorides / Sulfones / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides
show 2 more
Substituents
3-phenylpyridine / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenesulfonyl group / Benzenoid / Bipyridine / Heteroaromatic compound / Hydrocarbon derivative
show 12 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfone, organochlorine compound, bipyridines (CHEBI:6339)

Chemical Identifiers

UNII
WRX4NFY03R
CAS number
202409-33-4
InChI Key
MNJVRJDLRVPLFE-UHFFFAOYSA-N
InChI
InChI=1S/C18H15ClN2O2S/c1-12-3-4-14(10-20-12)18-17(9-15(19)11-21-18)13-5-7-16(8-6-13)24(2,22)23/h3-11H,1-2H3
IUPAC Name
5-chloro-3-(4-methanesulfonylphenyl)-2-(6-methylpyridin-3-yl)pyridine
SMILES
CC1=NC=C(C=C1)C1=C(C=C(Cl)C=N1)C1=CC=C(C=C1)S(C)(=O)=O

References

Synthesis Reference

Andrea Castellin, Paolo Stabile, Francesco Fontana, Ottorino De Lucchi, Andrea Caporale, Stefano Tartaggia, "PROCESS FOR PREPARING 1-(6-METHYLPYRIDIN-3-YL)-2-[4-(METHYLSULFONYL)PHENYL]ETHANONE, AN INTERMEDIATE OF ETORICOXIB." U.S. Patent US20120232281, issued September 13, 2012.

US20120232281
General References
Not Available
Human Metabolome Database
HMDB0015565
KEGG Drug
D03710
KEGG Compound
C11718
PubChem Compound
123619
PubChem Substance
46504505
ChemSpider
110209
BindingDB
50072064
RxNav
307296
ChEBI
6339
ChEMBL
CHEMBL416146
ZINC
ZINC000000579472
Therapeutic Targets Database
DAP000738
PharmGKB
PA164776853
PDBe Ligand
5CH
Wikipedia
Etoricoxib
PDB Entries
3cfl

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceRheumatoid Arthritis1
4CompletedPreventionFasting / Fasting Headache / Headache / Ramadan Headache1
4CompletedPreventionOssification, Heterotopic1
4CompletedTreatmentAchilles Tendinopathy1
4CompletedTreatmentAcute Gouty Arthritis1
4CompletedTreatmentBack Pain Lower Back Chronic1
4CompletedTreatmentCyclooxygenase Two Inhibitors / Etoricoxib / Periodontitis / Saliva / Superoxide Dismutase1
4CompletedTreatmentKnee Arthroscopy1
4CompletedTreatmentLaparoscopic Surgery for Appendicitis / Laparoscopic Surgery for Cholecystitis / Laparoscopic Surgery for Ovarian Cysts1
4CompletedTreatmentOsteoarthritis (OA)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral90 MG
Tablet, film coatedOral120 MG
Tablet, film coatedOral30 MG
Tablet
Tablet, film coatedOral60 MG
Tablet, coatedOral30 mg
TabletOral120 mg
TabletOral60 mg
Tablet, coatedOral120 mg
TabletOral90 mg
Tablet, delayed releaseOral60 mg
Tablet, film coatedOral
Tablet, coatedOral60 mg
Tablet, coatedOral90 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00328 mg/mLALOGPS
logP3.7ALOGPS
logP2.79ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)19.69ChemAxon
pKa (Strongest Basic)4.96ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area59.92 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity95.04 m3·mol-1ChemAxon
Polarizability36.42 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9776
Blood Brain Barrier+0.9399
Caco-2 permeable+0.8866
P-glycoprotein substrateNon-substrate0.845
P-glycoprotein inhibitor INon-inhibitor0.7624
P-glycoprotein inhibitor IINon-inhibitor0.9869
Renal organic cation transporterNon-inhibitor0.8267
CYP450 2C9 substrateNon-substrate0.6702
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.506
CYP450 1A2 substrateInhibitor0.6415
CYP450 2C9 inhibitorInhibitor0.8528
CYP450 2D6 inhibitorNon-inhibitor0.9268
CYP450 2C19 inhibitorInhibitor0.9087
CYP450 3A4 inhibitorInhibitor0.585
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8848
Ames testNon AMES toxic0.7952
CarcinogenicityNon-carcinogens0.6856
BiodegradationNot ready biodegradable0.9961
Rat acute toxicity2.4100 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9934
hERG inhibition (predictor II)Non-inhibitor0.8582
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Capone ML, Tacconelli S, Di Francesco L, Sacchetti A, Sciulli MG, Patrignani P: Pharmacodynamic of cyclooxygenase inhibitors in humans. Prostaglandins Other Lipid Mediat. 2007 Jan;82(1-4):85-94. Epub 2006 Jul 3. [PubMed:17164136]
  4. FitzGerald GA: COX-2 in play at the AHA and the FDA. Trends Pharmacol Sci. 2007 Jul;28(7):303-7. Epub 2007 Jun 18. [PubMed:17573128]
  5. Yuan Y, Hunt RH: Global gastrointestinal safety profile of etoricoxib and lumiracoxib. Curr Pharm Des. 2007;13(22):2237-47. [PubMed:17691997]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Takemoto JK, Reynolds JK, Remsberg CM, Vega-Villa KR, Davies NM: Clinical pharmacokinetic and pharmacodynamic profile of etoricoxib. Clin Pharmacokinet. 2008;47(11):703-20. [PubMed:18840026]
  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:19515014]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Data based on findings of in vitro studies.
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Kassahun K, McIntosh IS, Shou M, Walsh DJ, Rodeheffer C, Slaughter DE, Geer LA, Halpin RA, Agrawal N, Rodrigues AD: Role of human liver cytochrome P4503A in the metabolism of etoricoxib, a novel cyclooxygenase-2 selective inhibitor. Drug Metab Dispos. 2001 Jun;29(6):813-20. [PubMed:11353749]
  2. Etoricoxib FDA label [File]
  3. EMA Etoricoxib Assessment [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
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:19515014]
  2. Lin LY, Di Stefano EW, Schmitz DA, Hsu L, Ellis SW, Lennard MS, Tucker GT, Cho AK: Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6. Drug Metab Dispos. 1997 Sep;25(9):1059-64. [PubMed:9311621]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Kassahun K, McIntosh IS, Shou M, Walsh DJ, Rodeheffer C, Slaughter DE, Geer LA, Halpin RA, Agrawal N, Rodrigues AD: Role of human liver cytochrome P4503A in the metabolism of etoricoxib, a novel cyclooxygenase-2 selective inhibitor. Drug Metab Dispos. 2001 Jun;29(6):813-20. [PubMed:11353749]
  2. Etoricoxib FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Kassahun K, McIntosh IS, Shou M, Walsh DJ, Rodeheffer C, Slaughter DE, Geer LA, Halpin RA, Agrawal N, Rodrigues AD: Role of human liver cytochrome P4503A in the metabolism of etoricoxib, a novel cyclooxygenase-2 selective inhibitor. Drug Metab Dispos. 2001 Jun;29(6):813-20. [PubMed:11353749]
  2. Medhi B, Sukhija M, Prakash A, Gaikwad S, Bansal V, Pandhi P: Effects of etoricoxib on the pharmacokinetics of phenytoin. Pharmacol Rep. 2008 Mar-Apr;60(2):233-7. [PubMed:18443385]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Kassahun K, McIntosh IS, Shou M, Walsh DJ, Rodeheffer C, Slaughter DE, Geer LA, Halpin RA, Agrawal N, Rodrigues AD: Role of human liver cytochrome P4503A in the metabolism of etoricoxib, a novel cyclooxygenase-2 selective inhibitor. Drug Metab Dispos. 2001 Jun;29(6):813-20. [PubMed:11353749]

Drug created on August 30, 2007 09:49 / Updated on June 12, 2020 10:51

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