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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
Chlortenoxicam
Lornoxicamum
External Identifiers
  • CCRIS 8589
  • Ro 13-9297
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LorcamTaisho Pharmaceutical Co.
XafonNycomed
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIER09126G7A
CAS number70374-39-9
WeightAverage: 371.81
Monoisotopic: 370.9801259
Chemical FormulaC13H10ClN3O4S2
InChI KeyWLHQHAUOOXYABV-UHFFFAOYSA-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/h2-6,18H,1H3,(H,15,16,19)
IUPAC Name
SMILES
CN1C(C(=O)NC2=CC=CC=N2)=C(O)C2=C(C=C(Cl)S2)S1(=O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids and derivatives
Alternative Parents
Substituents
  • Alpha-amino acid or derivatives
  • Thienothiazine
  • N-arylamide
  • 2,3,5-trisubstituted thiophene
  • Ortho-thiazine
  • Aryl chloride
  • Aryl halide
  • Pyridine
  • Organosulfonic acid amide
  • Imidolactam
  • Heteroaromatic compound
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Thiophene
  • Vinylogous acid
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.9964
Blood Brain Barrier-0.964
Caco-2 permeable+0.7528
P-glycoprotein substrateSubstrate0.5511
P-glycoprotein inhibitor INon-inhibitor0.8209
P-glycoprotein inhibitor IINon-inhibitor0.8506
Renal organic cation transporterNon-inhibitor0.9132
CYP450 2C9 substrateSubstrate0.6831
CYP450 2D6 substrateNon-substrate0.8868
CYP450 3A4 substrateNon-substrate0.6652
CYP450 1A2 substrateNon-inhibitor0.7958
CYP450 2C9 inhibitorInhibitor0.7138
CYP450 2D6 inhibitorNon-inhibitor0.8714
CYP450 2C19 inhibitorNon-inhibitor0.7777
CYP450 3A4 inhibitorNon-inhibitor0.8755
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7815
Ames testNon AMES toxic0.8009
CarcinogenicityNon-carcinogens0.6844
BiodegradationNot ready biodegradable0.9851
Rat acute toxicity3.8570 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9494
hERG inhibition (predictor II)Non-inhibitor0.8681
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP2.62BIOBYTE STARLIST (2009)
Predicted Properties
PropertyValueSource
Water Solubility0.0437 mg/mLALOGPS
logP3.08ALOGPS
logS-3.9ALOGPS
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  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:8706598 ]
  2. Vane JR: Introduction: mechanism of action of NSAIDs. Br J Rheumatol. 1996 Apr;35 Suppl 1:1-3. [PubMed:8630629 ]
  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:12879104 ]
  4. Skjodt NM, Davies NM: Clinical pharmacokinetics of lornoxicam. A short half-life oxicam. Clin Pharmacokinet. 1998 Jun;34(6):421-8. [PubMed:9646006 ]
  5. Olkkola KT, Brunetto AV, Mattila MJ: Pharmacokinetics of oxicam nonsteroidal anti-inflammatory agents. Clin Pharmacokinet. 1994 Feb;26(2):107-20. [PubMed:8162655 ]
  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:2284217 ]
  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:2284216 ]
  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:8857077 ]
External Links
ATC CodesM01AC05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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 gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
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. doi: 10.1016/j.contraception.2009.12.008. Epub 2010 Jan 27. [PubMed:20399943 ]
  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:10450786 ]
  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:17516707 ]
  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:11846620 ]
Kind
Protein
Organism
Human
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 brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
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. doi: 10.1016/j.contraception.2009.12.008. Epub 2010 Jan 27. [PubMed:20399943 ]
  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:10450786 ]
  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:17516707 ]
  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:11846620 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 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, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. 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:16118328 ]
  2. 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:17022718 ]
  3. 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:15606435 ]
  4. 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:10640513 ]
  5. 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:8857077 ]
  6. 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 ]
  7. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  8. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
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Drug created on August 18, 2010 12:12 / Updated on May 11, 2016 10:28