Identification

Name
Lornoxicam
Accession Number
DB06725
Type
Small Molecule
Groups
Approved, Investigational
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
  • lornoxicam
  • Lornoxicamum
External IDs
CCRIS 8589 / Ro 13-9297
International/Other Brands
Lorcam (Taisho Pharmaceutical Co.) / Xafon (Nycomed)
Categories
UNII
ER09126G7A
CAS number
70374-39-9
Weight
Average: 371.81
Monoisotopic: 370.9801259
Chemical Formula
C13H10ClN3O4S2
InChI Key
WLHQHAUOOXYABV-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
6-chloro-4-hydroxy-2-methyl-1,1-dioxo-N-(pyridin-2-yl)-2H-1λ⁶-thieno[2,3-e][1,2]thiazine-3-carboxamide
SMILES
CN1C(C(=O)NC2=CC=CC=N2)=C(O)C2=C(C=C(Cl)S2)S1(=O)=O

Pharmacology

Indication

For the treatment of acute mild to moderate pain, as well as pain and inflammation of the joints caused by certain types of rheumatic diseases.

Pharmacodynamics

Lornoxicam 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 action

Like 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.

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

Lornoxicam is absorbed rapidly and almost completely from the GI tract (90-100%).

Volume of distribution
Not Available
Protein binding

Lornoxicam 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.

Route of elimination
Not Available
Half life

3-5 hours

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of gastrointestinal bleeding can be increased when Lornoxicam is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of gastrointestinal bleeding can be increased when Lornoxicam is combined with (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Lornoxicam is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
4-hydroxycoumarinThe risk or severity of gastrointestinal bleeding can be increased when Lornoxicam is combined with 4-hydroxycoumarin.
AbacavirLornoxicam may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Lornoxicam is combined with Abciximab.
AbirateroneThe metabolism of Lornoxicam can be decreased when combined with Abiraterone.
AcarboseLornoxicam may decrease the excretion rate of Acarbose which could result in a higher serum level.
AcebutololLornoxicam may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Lornoxicam is combined with Aceclofenac.
Food Interactions
Not Available

References

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
KEGG Drug
D01866
PubChem Compound
54690031
PubChem Substance
99443271
ChemSpider
10442760
BindingDB
92331
ChEBI
31783
ChEMBL
CHEMBL1569487
PharmGKB
PA165958395
Wikipedia
Lornoxicam
ATC Codes
M01AC05 — Lornoxicam

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedPreventionPost Operative Endodontic Pain1
2CompletedTreatmentBunionectomy / Orthopedic Procedures1
2CompletedTreatmentHeadache (Migraine)1
2TerminatedTreatmentAlzheimer's Disease (AD)1
3CompletedTreatmentPostoperative pain1
3Unknown StatusPreventionInguinal Hernias / Postoperative pain1
4CompletedTreatmentAcute Coronary Syndromes (ACS)1
4CompletedTreatmentPostoperative pain1
4RecruitingTreatmentBacillus Calmette-Guerin (BCG) Cystitis / Intra-vesical Instillation / Non-Muscle-invasive Bladder Cancer (NMIBC)1
Not AvailableCompletedTreatmentKnee Osteoarthritis (Knee OA)1
Not AvailableCompletedTreatmentOsteoarthritis of the Knee Joint1
Not AvailableUnknown StatusTreatmentPain NOS1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.62BIOBYTE STARLIST (2009)
Predicted Properties
PropertyValueSource
Water Solubility0.0437 mg/mLALOGPS
logP3.08ALOGPS
logP0.64ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)1.82ChemAxon
pKa (Strongest Basic)4.22ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area99.6 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity87.9 m3·mol-1ChemAxon
Polarizability33.3 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-2619000000-b00c34491f32edc2be89
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-4920000000-9f82e448f745973a1607

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acids and derivatives
Alternative Parents
Thienothiazines / 2,3,5-trisubstituted thiophenes / N-arylamides / 1,2-thiazines / Aryl chlorides / Imidolactams / Organosulfonamides / Pyridines and derivatives / Vinylogous acids / Heteroaromatic compounds
show 7 more
Substituents
Alpha-amino acid or derivatives / Thienothiazine / N-arylamide / 2,3,5-trisubstituted thiophene / Ortho-thiazine / Aryl chloride / Aryl halide / Organosulfonic acid amide / Pyridine / Imidolactam
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monocarboxylic acid amide, organochlorine compound, pyridines, heteroaryl hydroxy compound, thienothiazine (CHEBI:31783)

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 gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
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...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
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
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. 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. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  7. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Drug created on August 18, 2010 12:12 / Updated on November 02, 2018 06:19