Lumiracoxib

Identification

Generic Name
Lumiracoxib
DrugBank Accession Number
DB01283
Background

Lumiracoxib is a COX-2 selective non-steroidal anti-inflammatory drug (NSAID). On August 11, 2007, Australia's Therapeutic Goods Administration (TGA, the Australian equivalent of the FDA) cancelled the registration of lumiracoxib in Australia due to concerns that it may cause liver failure. New Zealand and Canada have also followed suit in recalling the drug.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 293.721
Monoisotopic: 293.061884577
Chemical Formula
C15H13ClFNO2
Synonyms
  • 2-((2-chloro-6-fluorophenyl)amino)-5-methylbenzeneacetic acid
  • Lumiracoxib
  • Lumiracoxibum
External IDs
  • COX 189
  • COX-189
  • COX189

Pharmacology

Indication

For the acute and chronic treatment of the signs and symptoms of osteoarthritis of the knee in adults.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Lumiracoxib has a different structure from the standard COX-2 inhibitors (e.g. celecoxib). It more closely resembles the structure of diclofenac (one chlorine substituted by fluorine, the phenylacetic acid has another methyl group in meta position), making it a member of the arylalkanoic acid family of NSAIDs. It binds to a different site on the COX-2 receptor than the standard COX-2 inhibitors. It displays extremely high COX-2 selectivity.

Mechanism of action

The mechanism of action of lumiracoxib is due to inhibition of prostaglandin synthesis via inhibition of cyclooygenase-2 (COX-2). Lumiracoxib does not inhibit COX-1 at therapeutic concentrations.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Humans
AProstaglandin G/H synthase 1
inhibitor
Humans
Absorption

Rapidly absorbed following oral administration, with an absolute oral bioavailablity of 74%.

Volume of distribution

Not Available

Protein binding

Highly bound to plasma proteins (>= 98%).

Metabolism

Hepatic oxidation and hydroxylation via CYP2C9. Three major metabolites have been identified in plasma: 4'-hydroxy-lumiracoxib, 5-carboxy-lumiracoxib, and 4'-hydroxy-5-carboxy-lumiracoxib.

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Route of elimination

Not Available

Half-life

Terminal half-life is approximately 4 hours.

Clearance

Not Available

Adverse Effects
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Toxicity

Single oral doses in mice and rats resulted in mortality and/or moribundity at doses of 600 mg/kg and 500 mg/kg, respectively. Single intraperitoneal doses in mice and rats results in mortality/moribundity at 750 mg/kg and 1000 mg/kg, respectively. The maximum non-lethal single oral and intraperitoneal dose in mouse was 300 mg/kg and 250 mg/kg, respectively. In the rat it was 150 mg/kg and 250 mg/kg, respectively.

Pathways
PathwayCategory
Lumiracoxib 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
AbacavirLumiracoxib may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe metabolism of Lumiracoxib can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Lumiracoxib is combined with Abciximab.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Lumiracoxib.
AcebutololLumiracoxib may decrease the antihypertensive activities of Acebutolol.
Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

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International/Other Brands
Prexige (Novartis)

Categories

ATC Codes
M01AH06 — Lumiracoxib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aminotoluenes. These are organic aromatic compounds containing a benzene that carries a single methyl group and one amino group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Toluenes
Direct Parent
Aminotoluenes
Alternative Parents
Aniline and substituted anilines / Fluorobenzenes / Chlorobenzenes / Aryl fluorides / Aryl chlorides / Amino acids / Secondary amines / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds
show 5 more
Substituents
Amine / Amino acid / Amino acid or derivatives / Aminotoluene / Aniline or substituted anilines / Aromatic homomonocyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Carbonyl group
show 17 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
organofluorine compound, monocarboxylic acid, organochlorine compound, secondary amino compound, amino acid (CHEBI:73044)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
V91T9204HU
CAS number
220991-20-8
InChI Key
KHPKQFYUPIUARC-UHFFFAOYSA-N
InChI
InChI=1S/C15H13ClFNO2/c1-9-5-6-13(10(7-9)8-14(19)20)18-15-11(16)3-2-4-12(15)17/h2-7,18H,8H2,1H3,(H,19,20)
IUPAC Name
2-{2-[(2-chloro-6-fluorophenyl)amino]-5-methylphenyl}acetic acid
SMILES
CC1=CC=C(NC2=C(Cl)C=CC=C2F)C(CC(O)=O)=C1

References

General References
Not Available
Human Metabolome Database
HMDB0015403
KEGG Drug
D03714
PubChem Compound
151166
PubChem Substance
46506378
ChemSpider
133236
BindingDB
50207446
ChEBI
73044
ChEMBL
CHEMBL404108
ZINC
ZINC000000007563
Therapeutic Targets Database
DAP000970
PharmGKB
PA164769031
PDBe Ligand
LUR
Wikipedia
Lumiracoxib
PDB Entries
4iiz / 4ik6 / 4oty / 4rrw / 4rrx / 4rrz

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentControlled Hypertension / Osteoarthritis (OA)1
4CompletedTreatmentGout Flares1
4CompletedTreatmentHealthy Volunteers (HV)1
4CompletedTreatmentMusculoskeletal Pain1
4CompletedTreatmentOsteoarthritis With Controlled Hypertension1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral200 mg
Tablet, film coatedOral400 mg
Tablet, film coatedOral100 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP3.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00549 mg/mLALOGPS
logP4.56ALOGPS
logP4.31Chemaxon
logS-4.7ALOGPS
pKa (Strongest Acidic)4.11Chemaxon
pKa (Strongest Basic)-1.3Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area49.33 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity75.91 m3·mol-1Chemaxon
Polarizability28.54 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9825
Blood Brain Barrier+0.9715
Caco-2 permeable+0.818
P-glycoprotein substrateNon-substrate0.7336
P-glycoprotein inhibitor INon-inhibitor0.7134
P-glycoprotein inhibitor IINon-inhibitor0.9389
Renal organic cation transporterNon-inhibitor0.916
CYP450 2C9 substrateNon-substrate0.7247
CYP450 2D6 substrateNon-substrate0.8639
CYP450 3A4 substrateNon-substrate0.5964
CYP450 1A2 substrateInhibitor0.5208
CYP450 2C9 inhibitorInhibitor0.6844
CYP450 2D6 inhibitorNon-inhibitor0.8163
CYP450 2C19 inhibitorNon-inhibitor0.8576
CYP450 3A4 inhibitorNon-inhibitor0.8063
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6222
Ames testNon AMES toxic0.8453
CarcinogenicityNon-carcinogens0.6326
BiodegradationNot ready biodegradable0.9954
Rat acute toxicity3.5160 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9512
hERG inhibition (predictor II)Non-inhibitor0.7169
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-MSsplash10-0002-2290000000-3dc98edbc540838a7548
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004l-0090000000-5085ee66094b4f002cf7
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0090000000-e8b6733f03a88fcff16f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-002e-0090000000-58840747e86af48a14ad
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001l-5090000000-107f858c1fd356762ef2
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-05fs-0960000000-bddf16ec1a5bccb6282b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9260000000-c62003ad672fe4575993
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-170.8362821
predicted
DarkChem Lite v0.1.0
[M-H]-165.29262
predicted
DeepCCS 1.0 (2019)
[M+H]+171.4655821
predicted
DarkChem Lite v0.1.0
[M+H]+167.65062
predicted
DeepCCS 1.0 (2019)
[M+Na]+171.1742821
predicted
DarkChem Lite v0.1.0
[M+Na]+173.74388
predicted
DeepCCS 1.0 (2019)

Targets

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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. Capone ML, Tacconelli S, Sciulli MG, Patrignani P: Clinical pharmacology of selective COX-2 inhibitors. Int J Immunopathol Pharmacol. 2003 May-Aug;16(2 Suppl):49-58. [Article]
  2. Tacconelli S, Capone ML, Patrignani P: Clinical pharmacology of novel selective COX-2 inhibitors. Curr Pharm Des. 2004;10(6):589-601. [Article]
  3. Atherton C, Jones J, McKaig B, Bebb J, Cunliffe R, Burdsall J, Brough J, Stevenson D, Bonner J, Rordorf C, Scott G, Branson J, Hawkey CJ: Pharmacology and gastrointestinal safety of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor: An integrated study. Clin Gastroenterol Hepatol. 2004 Feb;2(2):113-20. [Article]
  4. Kalbag J, Yeh CM, Milosavljev S, Lasseter K, Oberstein S, Rordorf C: No influence of moderate hepatic impairment on the pharmacokinetics of lumiracoxib, an oral COX-2 selective inhibitor. Pharmacol Res. 2004 Aug;50(2):181-6. [Article]
  5. Esser R, Berry C, Du Z, Dawson J, Fox A, Fujimoto RA, Haston W, Kimble EF, Koehler J, Peppard J, Quadros E, Quintavalla J, Toscano K, Urban L, van Duzer J, Zhang X, Zhou S, Marshall PJ: Preclinical pharmacology of lumiracoxib: a novel selective inhibitor of cyclooxygenase-2. Br J Pharmacol. 2005 Feb;144(4):538-50. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
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. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Capone ML, Tacconelli S, Sciulli MG, Patrignani P: Clinical pharmacology of selective COX-2 inhibitors. Int J Immunopathol Pharmacol. 2003 May-Aug;16(2 Suppl):49-58. [Article]
  2. Esser R, Berry C, Du Z, Dawson J, Fox A, Fujimoto RA, Haston W, Kimble EF, Koehler J, Peppard J, Quadros E, Quintavalla J, Toscano K, Urban L, van Duzer J, Zhang X, Zhou S, Marshall PJ: Preclinical pharmacology of lumiracoxib: a novel selective inhibitor of cyclooxygenase-2. Br J Pharmacol. 2005 Feb;144(4):538-50. [Article]
  3. Jermany J, Branson J, Schmouder R, Guillaume M, Rordorf C: Lumiracoxib does not affect the ex vivo antiplatelet aggregation activity of low-dose aspirin in healthy subjects. J Clin Pharmacol. 2005 Oct;45(10):1172-8. [Article]
  4. Warner TD, Vojnovic I, Bishop-Bailey D, Mitchell JA: Influence of plasma protein on the potencies of inhibitors of cyclooxygenase-1 and -2. FASEB J. 2006 Mar;20(3):542-4. Epub 2006 Jan 10. [Article]
  5. Blobaum AL, Marnett LJ: Molecular determinants for the selective inhibition of cyclooxygenase-2 by lumiracoxib. J Biol Chem. 2007 Jun 1;282(22):16379-90. Epub 2007 Apr 12. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. 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. [Article]
  2. Rordorf CM, Choi L, Marshall P, Mangold JB: Clinical pharmacology of lumiracoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet. 2005;44(12):1247-66. doi: 10.2165/00003088-200544120-00004. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 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. [Article]
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. Rordorf CM, Choi L, Marshall P, Mangold JB: Clinical pharmacology of lumiracoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet. 2005;44(12):1247-66. doi: 10.2165/00003088-200544120-00004. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. 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. [Article]
  2. Rordorf CM, Choi L, Marshall P, Mangold JB: Clinical pharmacology of lumiracoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet. 2005;44(12):1247-66. doi: 10.2165/00003088-200544120-00004. [Article]

Drug created at May 17, 2007 16:57 / Updated at February 21, 2021 18:51