Banner
Identification
Name Meloxicam
Accession Number DB00814 (APRD00529)
Type small molecule
Groups approved
Description

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve the symptoms of arthritis, primary dysmenorrhea, fever; and as an analgesic, especially where there is an inflammatory component. It is closely related to piroxicam. In Europe it is marketed under the brand names Movalis, Melox, and Recoxa. In North America it is generally marketed under the brand name Mobic. In Latin America, the drug is marketed as Tenaron. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Meloxicamum [latin]
Brand names
  • Apo-meloxicam
  • Co Meloxicam
  • Dom-meloxicam
  • Gen-meloxicam
  • Metacam
  • Mobic
  • Mobicox
  • Movalis
  • Movatec
  • Novo-meloxicam
  • Parocin
  • PHL-meloxicam
  • PMS-meloxicam
  • Ratio-meloxicam
  • Tenaron
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents
  • Cyclooxygenase Inhibitors
  • Antiemetics
  • Analgesics
  • Growth Inhibitors
  • Nonsteroidal Anti-inflammatory Agents (NSAIAs)
CAS number 71125-38-7
Weight Average: 351.401
Monoisotopic: 351.034747299
Chemical Formula C14H13N3O4S2
InChI Key InChIKey=ZRVUJXDFFKFLMG-UHFFFAOYSA-N
InChI
InChI=1S/C14H13N3O4S2/c1-8-7-15-14(22-8)16-13(19)11-12(18)9-5-3-4-6-10(9)23(20,21)17(11)2/h3-7,18H,1-2H3,(H,15,16,19)
Plain Text
IUPAC Name
4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-2H-1$l^{6},2-benzothiazine-3-carboxamide
SMILES
CN1C(C(=O)NC2=NC=C(C)S2)=C(O)C2=C(C=CC=C2)S1(=O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzenesulfonamides
  • Phenethylamines
Substructures
  • Hydroxy Compounds
  • Amino Ketones
  • Sulfonyls
  • Benzene and Derivatives
  • Benzenesulfonamides
  • Thiazoles
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Sulfonamides
  • Benzoyl Derivatives
  • Ketones
Pharmacology
Indication For symptomatic treatment of arthritis and osteoarthritis.
Pharmacodynamics Meloxicam is an nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Prostaglandins are substances that contribute to inflammation of joints. Meloxicam inhibits prostaglandin synthetase (cylooxygenase 1 and 2) and leads to a decrease of the synthesis of prostaglandins, therefore, inflammation is reduced.
Mechanism of action Anti-inflammatory effects of meloxicam are believed to be due to inhibition of prostaglandin synthetase (cylooxygenase), leading to the inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, inhibition of their synthesis may be associated with the analgesic and antipyretic effects of meloxicam.
Absorption Absolute bioavailability = 89%
Volume of distribution
  • 10 L
Protein binding 99.4% bound, primarily to albumin
Metabolism

Meloxicam is almost completely metabolized into inactive metabolites by the cytochrome P450 (CYP450) isozymes. CYP2C9 is primarily responsible for metabolism of meloxicam while CYP3A4 plays a minor role. An intermediate metabolite, 5'-hydroxymethyl meloxicam, is further metabolized to 5'-carboxy meloxicam, the major metabolite. Peroxidase activity is thought to produce the two other inactive metabolites of meloxicam.

Route of elimination Meloxicam is almost completely metabolized to four pharmacologically inactive metabolites. Meloxicam excretion is predominantly in the form of metabolites, and occurs to equal extents in the urine and feces. Only traces of the unchanged parent compound are excreted in the urine (0.2%) and feces (1.6%). The extent of the urinary excretion was confirmed for unlabeled multiple 7.5 mg doses: 0.5%, 6% and 13% of the dose were found in urine in the form of meloxicam, and the 5'-hydroxymethyl and 5'-carboxy metabolites, respectively.
Half life 15-20 hours
Clearance
  • 8.8 mL/min [Healthy Male Adults (Fed) oral 7.5 mg tablets]
  • 9.9 mL/min [Eldery Male (Fed) oral 15 mg capsules]
  • 5.1 mL/min [Eldery Female (Fed) oral 15 mg capsules]
  • 19 mL/min [Renal Failure (Fasted) oral 15 mg capsules]
  • 11 mL/min [Hepatic Insufficiency (Fasted) oral 15 mg capsules]
Toxicity LD50, Acute: 84 mg/kg (Rat); Oral 470 mg/kg (Mouse); Oral 320 mg/kg (Rabbit)
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00106 Meloxicam Pathway SMP00106
Pharmacoeconomics
Manufacturers
  • Boehringer ingelheim pharmaceuticals inc
  • Actavis totowa llc
  • Apotex inc etobicoke site
  • Aurobindo pharma ltd
  • Beijing double crane pharmaceutical co ltd
  • Beijing yabao biopharmaceutical co ltd
  • Breckenridge pharmaceutical inc
  • Caraco pharmaceutical laboratories ltd
  • Carlsbad technology inc
  • Corepharma llc
  • Dr reddys laboratories inc
  • Genpharm inc
  • Glenmark generics ltd
  • Lupin pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Roxane laboratories inc
  • Strides arcolab ltd
  • Taro pharmaceutical industries ltd
  • Teva pharmaceuticals usa
  • Unichem laboratories ltd
  • Watson laboratories inc
  • Zydus pharmaceuticals usa inc
Packagers
Dosage forms
Form Route Strength
Suspension Oral 7.5 mg/5 ml
Tablet Oral 15 mg
Tablet Oral 7.5 mg
Prices
Unit description Cost Unit
Meloxicam 7.5 mg/5ml Suspension 100ml Bottle 86.99 USD bottle
Meloxicam bp powder 56.61 USD g
Mobic 15 mg tablet 7.37 USD tablet
Meloxicam 15 mg tablet 4.94 USD tablet
Mobic 7.5 mg tablet 4.74 USD tablet
Meloxicam 7.5 mg tablet 3.23 USD tablet
Patents
Country Patent Number Approved Expires
United States 6184220 1999-09-25 2019-09-25
Properties
State solid
Melting point 254 oC
Experimental Properties
Property Value Source
water solubility 7.15 mg/L PhysProp
logP 1.9 PhysProp
Caco2 permeability -4.71 [ADME Research, USCD] BiGG
pKa 4.08 Various sources
Predicted Properties
Property Value Source
water solubility 1.54e-01 g/l ALOGPS
logP 2.28 ALOGPS
logP 1.60 ChemAxon Molconvert
logS -3.36 ALOGPS
pKa 10.64 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 99.60 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 88.62 ChemAxon Molconvert
polarizability 34.25 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00969 Link_out
KEGG Compound C08169 Link_out
PubChem Compound 5281106 Link_out
PubChem Substance 46506624 Link_out
ChemSpider 4444553 Link_out
BindingDB 50056998 Link_out
Therapeutic Targets Database DAP000971 Link_out
PharmGKB PA450353 Link_out
Drug Product Database 2248031 Link_out
RxList http://www.rxlist.com/cgi/generic/mobic.htm Link_out
Drugs.com http://www.drugs.com/cdi/meloxicam.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Meloxicam Link_out
ATC Codes
  • M01AC06
AHFS Codes
  • 28:08.04.92
PDB Entries Not Available
FDA label show (45.4 KB)
MSDS show (35.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Prostaglandin G/H synthase 2

Pharmacological action: yes
Actions: inhibitor

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

Organism class: human
UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Poulsen Nautrup B, Horstermann D: [Pharmacodynamic and pharmacokinetic aspects of the non-inflammatory non-steroidal agent meloxicam in dogs] Dtsch Tierarztl Wochenschr. 1999 Mar;106(3):94-100. Pubmed
  2. Tegeder I, Lotsch J, Krebs S, Muth-Selbach U, Brune K, Geisslinger G: Comparison of inhibitory effects of meloxicam and diclofenac on human thromboxane biosynthesis after single doses and at steady state. Clin Pharmacol Ther. 1999 May;65(5):533-44. Pubmed
  3. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73. Pubmed
  4. Panara MR, Renda G, Sciulli MG, Santini G, Di Giamberardino M, Rotondo MT, Tacconelli S, Seta F, Patrono C, Patrignani P: Dose-dependent inhibition of platelet cyclooxygenase-1 and monocyte cyclooxygenase-2 by meloxicam in healthy subjects. J Pharmacol Exp Ther. 1999 Jul;290(1):276-80. Pubmed
  5. Gross JM, Dwyer JE, Knox FG: Natriuretic response to increased pressure is preserved with COX-2 inhibitors. Hypertension. 1999 Nov;34(5):1163-7. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostaglandin G/H synthase 1

Pharmacological action: unknown
Actions: inhibitor

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

Organism class: human
UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73. Pubmed
  2. Panara MR, Renda G, Sciulli MG, Santini G, Di Giamberardino M, Rotondo MT, Tacconelli S, Seta F, Patrono C, Patrignani P: Dose-dependent inhibition of platelet cyclooxygenase-1 and monocyte cyclooxygenase-2 by meloxicam in healthy subjects. J Pharmacol Exp Ther. 1999 Jul;290(1):276-80. Pubmed
Enzymes

1. Cytochrome P450 2C9

Actions: substrate, inhibitor

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, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chesne C, Guyomard C, Guillouzo A, Schmid J, Ludwig E, Sauter T: Metabolism of Meloxicam in human liver involves cytochromes P4502C9 and 3A4. Xenobiotica. 1998 Jan;28(1):1-13. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Ludwig E, Schmid J, Beschke K, Ebner T: Activation of human cytochrome P-450 3A4-catalyzed meloxicam 5’-methylhydroxylation by quinidine and hydroquinidine in vitro. J Pharmacol Exp Ther. 1999 Jul;290(1):1-8. Pubmed
  4. 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
  5. 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

2. Cytochrome P450 3A4

Actions: substrate

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chesne C, Guyomard C, Guillouzo A, Schmid J, Ludwig E, Sauter T: Metabolism of Meloxicam in human liver involves cytochromes P4502C9 and 3A4. Xenobiotica. 1998 Jan;28(1):1-13. Pubmed
  2. Ludwig E, Schmid J, Beschke K, Ebner T: Activation of human cytochrome P-450 3A4-catalyzed meloxicam 5’-methylhydroxylation by quinidine and hydroquinidine in vitro. J Pharmacol Exp Ther. 1999 Jul;290(1):1-8. Pubmed
  3. 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

3. 6-phosphogluconate dehydrogenase, decarboxylating

Actions: inhibitor

6-phospho-D-gluconate + NADP(+) = D-ribulose 5-phosphate + CO(2) + NADPH

UniProt ID: P52209 Link_out
Gene: PGD Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Mar 17. Pubmed
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

4. Cytochrome P450 2C8

Actions: substrate, inhibitor

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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
Transporters

1. Multidrug resistance-associated protein 4

Actions: substrate

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Uchida Y, Kamiie J, Ohtsuki S, Terasaki T: Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96. Epub 2007 Oct 16. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:43

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.