You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameLornoxicam
Accession NumberDB06725
Typesmall molecule
Groupsapproved
Description

Lornoxicam (chlortenoxicam) is a new nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic, anti-inflammatory and antipyretic properties. Lornoxicam differs from other oxicam compounds in its potent inhibition of prostaglandin biosynthesis, a property that explains the particularly pronounced efficacy of the drug. Lornoxicam is approved for use in Japan.

Structure
Thumb
Synonyms
SynonymLanguageCode
AcabelNot AvailableNot Available
chlortenoxicamNot AvailableNot Available
CLTXNot AvailableNot Available
LorcamNot AvailableNot Available
Lorcam (TN)Not AvailableNot Available
LornoxicamumLatinINN
SafemNot AvailableNot Available
TaigalorNot AvailableNot Available
TelosNot AvailableNot Available
XEFONot AvailableNot Available
XefocamNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
LorcamTaisho Pharmaceutical Co.
XafonNycomed
Brand mixturesNot Available
Categories
CAS number70374-39-9
WeightAverage: 371.819
Monoisotopic: 370.98012491
Chemical FormulaC13H10ClN3O4S2
InChI KeyOXROWJKCGCOJDO-JLHYYAGUSA-N
InChI
InChI=1S/C13H10ClN3O4S2/c1-17-10(13(19)16-9-4-2-3-5-15-9)11(18)12-7(23(17,20)21)6-8(14)22-12/h2-6,19H,1H3,(H,15,16)/b13-10+
IUPAC Name
(3E)-6-chloro-3-{hydroxy[(pyridin-2-yl)amino]methylidene}-2-methyl-2H,3H,4H-1$l^{6},5,2-thieno[2,3-e][1$l^{6},2]thiazine-1,1,4-trione
SMILES
CN1\C(=C(\O)NC2=CC=CC=N2)C(=O)C2=C(C=C(Cl)S2)S1(=O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassThienothiazines
SubclassNot Available
Direct parentThienothiazines
Alternative parentsAminopyridines and Derivatives; Aryl Chlorides; Thiophenes; Sulfonamides; Ketones; Polyamines; Organochlorides
Substituentsaminopyridine; aryl chloride; aryl halide; pyridine; sulfonic acid derivative; sulfonamide; thiophene; ketone; polyamine; organochloride; carbonyl group; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the thienothiazines. These are heterocyclic compounds containing a thiophene ring fused to a thiazine.
Pharmacology
IndicationFor the treatment of acute mild to moderate pain, as well as pain and inflammation of the joints caused by certain types of rheumatic diseases.
PharmacodynamicsLornoxicam is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the oxicam class. As with other NSAIDS, lornoxicam is a potent inhibitor of the cyclooxgenase enzymes, which are responsible for catalyzing the formation of prostaglandins (act as messenger molecules in the process of inflammation) and thromboxane from arachidonic acid. Unlike some NSAIDS, lornoxicam's inhibition of cyclooxygenase does not lead to an increase in leukotriene formation, meaning that arachidonic acid is not moved to the 5-lipoxygenase cascade, resulting in the minimization of the risk of adverse events.
Mechanism of actionLike other NSAIDS, lornoxicam's anti-inflammatory and analgesic activity is related to its inhibitory action on prostaglandin and thromboxane synthesis through the inhibition of both COX-1 and COX-2. This leads to the reduction of inflammation, pain, fever, and swelling, which are mediated by prostaglandins. However, the exact mechanism of lornoxicam, like that of the other NSAIDs, has not been fully determined.
AbsorptionLornoxicam is absorbed rapidly and almost completely from the GI tract (90-100%).
Volume of distributionNot Available
Protein bindingLornoxicam is 99% bound to plasma proteins (almost exlusively to serum albumin).
Metabolism

Lornoxicam is metabolized completely by cyp 2C9 with the principal metabolite being 5'-hydroxy-lornoxicam and only negligible amounts of intact lornoxicam are excreted unchanged in the urine. Approximately 2/3 of the drug is eliminated via the liver and 1/3 via the kidneys in the active form.

SubstrateEnzymesProduct
Lornoxicam
5'-HydroxylornoxicamDetails
Route of eliminationNot Available
Half life3-5 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Lornoxicam Action PathwayDrug actionSMP00700
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9964
Blood Brain Barrier - 0.964
Caco-2 permeable + 0.7528
P-glycoprotein substrate Substrate 0.5511
P-glycoprotein inhibitor I Non-inhibitor 0.8209
P-glycoprotein inhibitor II Non-inhibitor 0.8506
Renal organic cation transporter Non-inhibitor 0.9132
CYP450 2C9 substrate Substrate 0.6831
CYP450 2D6 substrate Non-substrate 0.8868
CYP450 3A4 substrate Non-substrate 0.6652
CYP450 1A2 substrate Non-inhibitor 0.7958
CYP450 2C9 substrate Inhibitor 0.7138
CYP450 2D6 substrate Non-inhibitor 0.8714
CYP450 2C19 substrate Non-inhibitor 0.7777
CYP450 3A4 substrate Non-inhibitor 0.8755
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7815
Ames test Non AMES toxic 0.8009
Carcinogenicity Non-carcinogens 0.6844
Biodegradation Not ready biodegradable 0.9851
Rat acute toxicity 3.8570 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9494
hERG inhibition (predictor II) Non-inhibitor 0.8681
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
InjectionIntravenous4 mg/ml
TabletOral4 mg
TabletOral8 mg
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP2.62BIOBYTE STARLIST (2009)
Predicted Properties
PropertyValueSource
water solubility4.61e-02 g/lALOGPS
logP2.53ALOGPS
logP1.99ChemAxon
logS-3.9ALOGPS
pKa (strongest acidic)6.88ChemAxon
pKa (strongest basic)4.78ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count6ChemAxon
hydrogen donor count2ChemAxon
polar surface area99.6ChemAxon
rotatable bond count2ChemAxon
refractivity97.02ChemAxon
polarizability33.77ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Balfour JA, Fitton A, Barradell LB: Lornoxicam. A review of its pharmacology and therapeutic potential in the management of painful and inflammatory conditions. Drugs. 1996 Apr;51(4):639-57. Pubmed
  2. Vane JR: Introduction: mechanism of action of NSAIDs. Br J Rheumatol. 1996 Apr;35 Suppl 1:1-3. Pubmed
  3. Radhofer-Welte S, Rabasseda X: Lornoxicam, a new potent NSAID with an improved tolerability profile. Drugs Today (Barc). 2000 Jan;36(1):55-76. Pubmed
  4. Skjodt NM, Davies NM: Clinical pharmacokinetics of lornoxicam. A short half-life oxicam. Clin Pharmacokinet. 1998 Jun;34(6):421-8. Pubmed
  5. Olkkola KT, Brunetto AV, Mattila MJ: Pharmacokinetics of oxicam nonsteroidal anti-inflammatory agents. Clin Pharmacokinet. 1994 Feb;26(2):107-20. Pubmed
  6. Hitzenberger G, Radhofer-Welte S, Takacs F, Rosenow D: Pharmacokinetics of lornoxicam in man. Postgrad Med J. 1990;66 Suppl 4:S22-7. Pubmed
  7. Pruss TP, Stroissnig H, Radhofer-Welte S, Wendtlandt W, Mehdi N, Takacs F, Fellier H: Overview of the pharmacological properties, pharmacokinetics and animal safety assessment of lornoxicam. Postgrad Med J. 1990;66 Suppl 4:S18-21. Pubmed
  8. Bonnabry P, Leemann T, Dayer P: Role of human liver microsomal CYP2C9 in the biotransformation of lornoxicam. Eur J Clin Pharmacol. 1996;49(4):305-8. Pubmed
External Links
ResourceLink
KEGG DrugD01866
PubChem Compound5282204
PubChem Substance99443271
ChemSpider4445392
PharmGKBPA165958395
WikipediaLornoxicam
ATC CodesM01AC05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

  1. Renner RM, Jensen JT, Nichols MD, Edelman AB: Pain control in first-trimester surgical abortion: a systematic review of randomized controlled trials. Contraception. 2010 May;81(5):372-88. Epub 2010 Jan 27. Pubmed
  2. Berg J, Fellier H, Christoph T, Grarup J, Stimmeder D: The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro. Inflamm Res. 1999 Jul;48(7):369-79. Pubmed
  3. Rose P, Steinhauser C: Comparison of Lornoxicam and Rofecoxib in Patients with Activated Osteoarthritis (COLOR Study). Clin Drug Investig. 2004;24(4):227-36. Pubmed
  4. Bianchi M, Panerai AE: Effects of lornoxicam, piroxicam, and meloxicam in a model of thermal hindpaw hyperalgesia induced by formalin injection in rat tail. Pharmacol Res. 2002 Feb;45(2):101-5. Pubmed

2. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Renner RM, Jensen JT, Nichols MD, Edelman AB: Pain control in first-trimester surgical abortion: a systematic review of randomized controlled trials. Contraception. 2010 May;81(5):372-88. Epub 2010 Jan 27. Pubmed
  2. Berg J, Fellier H, Christoph T, Grarup J, Stimmeder D: The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro. Inflamm Res. 1999 Jul;48(7):369-79. Pubmed
  3. Rose P, Steinhauser C: Comparison of Lornoxicam and Rofecoxib in Patients with Activated Osteoarthritis (COLOR Study). Clin Drug Investig. 2004;24(4):227-36. Pubmed
  4. Bianchi M, Panerai AE: Effects of lornoxicam, piroxicam, and meloxicam in a model of thermal hindpaw hyperalgesia induced by formalin injection in rat tail. Pharmacol Res. 2002 Feb;45(2):101-5. Pubmed

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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
  3. 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
  4. Zhang Y, Zhong D, Si D, Guo Y, Chen X, Zhou H: Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype. Br J Clin Pharmacol. 2005 Jan;59(1):14-7. Pubmed
  5. Kohl C, Steinkellner M: Prediction of pharmacokinetic drug/drug interactions from In vitro data: interactions of the nonsteroidal anti-inflammatory drug lornoxicam with oral anticoagulants. Drug Metab Dispos. 2000 Feb;28(2):161-8. Pubmed
  6. Bonnabry P, Leemann T, Dayer P: Role of human liver microsomal CYP2C9 in the biotransformation of lornoxicam. Eur J Clin Pharmacol. 1996;49(4):305-8. Pubmed
  7. 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
  8. 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
comments powered by Disqus
Drug created on August 18, 2010 12:12 / Updated on September 16, 2013 18:04