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Identification
NamePiroxicam
Accession NumberDB00554  (APRD01187)
TypeSmall Molecule
GroupsApproved, Investigational
Description

A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
4-Hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazin-3-caboxyamid-1,1-dioxidNot AvailableNot Available
FeldeneNot AvailableNot Available
PiroxicamNot AvailableNot Available
PiroxicamumNot AvailableNot Available
PyroxycamNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
BruxicamNot Available
DolonexNot Available
ErazonNot Available
FeldenePfizer
GeldèneNot Available
ImprontalNot Available
RoxamBosnalijek
RoxidenNot Available
SasulenNot Available
SolocalmNot Available
TrastNot Available
Brand mixturesNot Available
Categories
CAS number36322-90-4
WeightAverage: 331.346
Monoisotopic: 331.062676609
Chemical FormulaC15H13N3O4S
InChI KeyQYSPLQLAKJAUJT-UHFFFAOYSA-N
InChI
InChI=1S/C15H13N3O4S/c1-18-13(15(20)17-12-8-4-5-9-16-12)14(19)10-6-2-3-7-11(10)23(18,21)22/h2-9,19H,1H3,(H,16,17,20)
IUPAC Name
4-hydroxy-2-methyl-1,1-dioxo-N-(pyridin-2-yl)-2H-1$l^{6},2-benzothiazine-3-carboxamide
SMILES
CN1C(C(=O)NC2=NC=CC=C2)=C(O)C2=C(C=CC=C2)S1(=O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzothiazines
SubclassNot Available
Direct parentBenzothiazines
Alternative parentsAminopyridines and Derivatives; Benzene and Substituted Derivatives; Sulfonamides; Secondary Carboxylic Acid Amides; Carboxylic Acids; Polyamines; Enolates
Substituentsaminopyridine; pyridine; benzene; sulfonamide; sulfonic acid derivative; carboxamide group; secondary carboxylic acid amide; enolate; carboxylic acid; polyamine; carboxylic acid derivative; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzothiazines. These are organic compounds containing a benzene fused to a thiazine ring (a six-member ring with four carbon atoms, one nitrogen atom and one sulfur atom).
Pharmacology
IndicationFor treatment of osteoarthritis and rheumatoid arthritis.
PharmacodynamicsPiroxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Piroxicam works by reducing hormones that cause inflammation and pain in the body. Piroxicam is used to reduce the pain, inflammation, and stiffness caused by rheumatoid arthritis and osteoarthritis.
Mechanism of actionThe antiinflammatory effect of Piroxicam may result from the reversible inhibition of cyclooxygenase, causing the peripheral inhibition of prostaglandin synthesis. The prostaglandins are produced by an enzyme called Cox-1. Piroxicam blocks the Cox-1 enzyme, resulting into the disruption of production of prostaglandins. Piroxicam also inhibits the migration of leukocytes into sites of inflammation and prevents the formation of thromboxane A2, an aggregating agent, by the platelets.
AbsorptionWell absorbed following oral administration.
Volume of distribution
  • 0.14 L/kg
Protein bindingNot Available
Metabolism

Renal

SubstrateEnzymesProduct
Piroxicam
5'-HydroxypiroxicamDetails
Route of eliminationPiroxicam and its biotransformation products are excreted in urine and feces, with about twice as much appearing in the urine as in the feces. Approximately 5% of a piroxicam dose is excreted unchanged. However, a substantial portion of piroxicam elimination occurs by hepatic metabolism. Piroxicam is excreted into human milk.
Half life30 to 86 hours
ClearanceNot Available
ToxicitySymptoms of overdose include drowsiness, nausea, stomach pain, and/or vomiting.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Piroxicam Action PathwayDrug actionSMP00077
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9898
Blood Brain Barrier - 0.9659
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.5786
P-glycoprotein inhibitor I Non-inhibitor 0.7285
P-glycoprotein inhibitor II Non-inhibitor 0.7453
Renal organic cation transporter Non-inhibitor 0.9437
CYP450 2C9 substrate Substrate 0.6437
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.7356
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Inhibitor 0.9086
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8789
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8709
Ames test Non AMES toxic 0.8767
Carcinogenicity Non-carcinogens 0.7612
Biodegradation Not ready biodegradable 0.923
Rat acute toxicity 3.1545 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9589
hERG inhibition (predictor II) Non-inhibitor 0.8311
Pharmacoeconomics
Manufacturers
  • Akorn inc
  • Pfizer laboratories div pfizer inc
  • Egis pharmaceuticals
  • Genpharm pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Nostrum laboratories inc
  • Roxane laboratories inc
  • Scs pharmaceuticals
  • Teva pharmaceuticals usa inc
  • Teva pharmaceuticals usa
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
SuppositoryRectal
TabletOral
Prices
Unit descriptionCostUnit
Piroxicam powder13.16USDg
Akten 3.5% drops7.5USDml
Feldene 20 mg capsule4.93USDcapsule
Feldene 10 mg capsule2.82USDcapsule
Piroxicam 20 mg capsule2.69USDcapsule
Pms-Piroxicam 20 mg Suppository1.82USDsuppository
Piroxicam 10 mg capsule1.44USDcapsule
Apo-Piroxicam 20 mg Capsule0.75USDcapsule
Novo-Pirocam 20 mg Capsule0.75USDcapsule
Nu-Pirox 20 mg Capsule0.75USDcapsule
Apo-Piroxicam 10 mg Capsule0.43USDcapsule
Gen-Piroxicam 10 mg Capsule0.43USDcapsule
Novo-Pirocam 10 mg Capsule0.43USDcapsule
Nu-Pirox 10 mg Capsule0.43USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point198-200 °CPhysProp
water solubility23 mg/L (at 22 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.06AVDEEF,A (1997)
logS-4.16ADME Research, USCD
Caco2 permeability-4.45ADME Research, USCD
pKa6.3SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.143ALOGPS
logP2.2ALOGPS
logP0.6ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)4.76ChemAxon
pKa (Strongest Basic)3.79ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area99.6 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity87.04 m3·mol-1ChemAxon
Polarizability32.27 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Paul D. Weeks, “3-Hydroxy 2-methyl benzisothiazolines as intermediates in production of piroxicam.” U.S. Patent US4376204, issued April, 1982.

US4376204
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00127
KEGG CompoundC01608
ChEBI8249
ChEMBLCHEMBL527
Therapeutic Targets DatabaseDAP000181
PharmGKBPA450985
Drug Product Database658839
RxListhttp://www.rxlist.com/cgi/generic/piroxicam.htm
Drugs.comhttp://www.drugs.com/cdi/piroxicam.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/fel1173.shtml
WikipediaPiroxicam
ATC CodesM01AC01M02AA07S01BC06
AHFS Codes
  • 28:08.04.92
PDB EntriesNot Available
FDA labelshow(74.3 KB)
MSDSshow(73.3 KB)
Interactions
Drug Interactions
Drug
AcebutololRisk of inhibition of renal prostaglandins
AcenocoumarolThe NSAID, piroxicam, may increase the anticoagulant effect of acenocoumarol.
AlendronateIncreased risk of gastric toxicity
AnisindioneThe NSAID, piroxicam, may increase the anticoagulant effect of anisindione.
AtenololRisk of inhibition of renal prostaglandins
Azilsartan medoxomilIncreases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
BetaxololNonsteroidal Anti-Inflammatory Agents such as piroxicam may diminish the antihypertensive effect of Beta-Blockers such as betaxolol. Monitor for increases in blood pressure if a nonsteroidal anti-inflammatory agent (NSAID) is initiated/dose increased, or decreases in blood pressure if a NSAID is discontinued/dose decreased; this is particularly important if NSAID treatment is for extended periods of time. Ophthalmic beta-blockers are likely of little concern.
BevantololRisk of inhibition of renal prostaglandins
BisoprololRisk of inhibition of renal prostaglandins
CarteololRisk of inhibition of renal prostaglandins
CarvedilolRisk of inhibition of renal prostaglandins
ColesevelamBile acid sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Monitor for decreased serum concentrations/therapeutic effects of nonsteroidal anti-inflammatory agents (NSAID) if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.
CyclosporineMonitor for nephrotoxicity
DicoumarolThe NSAID, piroxicam, may increase the anticoagulant effect of dicumarol.
EsmololRisk of inhibition of renal prostaglandins
Ginkgo bilobaAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
LabetalolRisk of inhibition of renal prostaglandins
LithiumThe NSAID, piroxicam, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
MethotrexateThe NSAID, piroxicam, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
MetoprololRisk of inhibition of renal prostaglandins
NadololRisk of inhibition of renal prostaglandins
OxprenololRisk of inhibition of renal prostaglandins
PenbutololRisk of inhibition of renal prostaglandins
PindololRisk of inhibition of renal prostaglandins
PractololRisk of inhibition of renal prostaglandins
PralatrexateNSAIDs increase the risk of toxicity due to impairment of renal clearance of pralatrexate thus increasing exposure. Monitor for adverse effects or adjust dose of pralatrexate.
PropranololRisk of inhibition of renal prostaglandins
RitonavirRitonavir increases the toxicity of piroxicam
SotalolRisk of inhibition of renal prostaglandins
TamoxifenPiroxicam may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Piroxicam is initiated, discontinued or dose changed.
TelmisartanConcomitant use of Telmisartan and Piroxicam may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
TimololRisk of inhibition of renal prostaglandins
TolbutamidePiroxicam, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Piroxicam is initiated, discontinued or dose changed.
TorasemidePiroxicam, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Piroxicam is initiated, discontinued or dose changed.
TrandolaprilThe NSAID, Piroxicam, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Piroxicam is initiated, discontinued or dose changed.
TreprostinilThe prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Piroxicam. Monitor for increased bleeding during concomitant thearpy.
TriflusalThe metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid (HTB), impairs the serum protein binding of glisentide to the same extent as acetylsalisylic acid. Thus, the free fraction of glisentide may be increased. A dosage reduction may be required if used in combination.
TrimethoprimThe strong CYP2C9 inhibitor, Piroxicam, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Piroxicam is initiated, discontinued or dose changed.
VilazodoneIncreased risk of bleeding with concomitant use of NSAIDs and vilazodone
VoriconazolePiroxicam, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if piroxicam is initiated, discontinued or dose changed.
WarfarinPiroxicam, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. The antiplatelet effect of piroxicam may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if piroxicam is initiated, discontinued or dose changed.
Food Interactions
  • Take with food. Avoid alcohol.

Targets

1. 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. 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. Bugajski J, Glod R, Gadek-Michalska A, Bugajski AJ: Involvement of constitutive (COX-1) and inducible cyclooxygenase (COX-2) in the adrenergic-induced ACTH and corticosterone secretion. J Physiol Pharmacol. 2001 Dec;52(4 Pt 2):795-809. Pubmed
  3. Fackovcova D, Kristova V, Kriska M: Renal damage induced by the treatment with non-opioid analgesics—theoretical assumption or clinical significance. Bratisl Lek Listy. 2000;101(8):417-22. Pubmed
  4. Raju J, Bird RP: Differential modulation of transforming growth factor-betas and cyclooxygenases in the platelet lysates of male F344 rats by dietary lipids and piroxicam. Mol Cell Biochem. 2002 Feb;231(1-2):139-46. Pubmed
  5. Veiga AP, Duarte ID, Avila MN, da Motta PG, Tatsuo MA, Francischi JN: Prevention by celecoxib of secondary hyperalgesia induced by formalin in rats. Life Sci. 2004 Oct 22;75(23):2807-17. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

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

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. Bugajski J, Glod R, Gadek-Michalska A, Bugajski AJ: Involvement of constitutive (COX-1) and inducible cyclooxygenase (COX-2) in the adrenergic-induced ACTH and corticosterone secretion. J Physiol Pharmacol. 2001 Dec;52(4 Pt 2):795-809. Pubmed
  3. Fackovcova D, Kristova V, Kriska M: Renal damage induced by the treatment with non-opioid analgesics—theoretical assumption or clinical significance. Bratisl Lek Listy. 2000;101(8):417-22. Pubmed
  4. Raju J, Bird RP: Differential modulation of transforming growth factor-betas and cyclooxygenases in the platelet lysates of male F344 rats by dietary lipids and piroxicam. Mol Cell Biochem. 2002 Feb;231(1-2):139-46. Pubmed
  5. Veiga AP, Duarte ID, Avila MN, da Motta PG, Tatsuo MA, Francischi JN: Prevention by celecoxib of secondary hyperalgesia induced by formalin in rats. Life Sci. 2004 Oct 22;75(23):2807-17. 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. 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
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Pelkonen O, Maenpaa J, Taavitsainen P, Rautio A, Raunio H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica. 1998 Dec;28(12):1203-53. Pubmed
  4. 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 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

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

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Bertucci C, Wainer IW: Improved chromatographic performance of a modified human albumin based stationary phase. Chirality. 1997;9(4):335-40. Pubmed

Transporters

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. Pubmed
  2. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. Pubmed
  3. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  4. Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. Pubmed
  5. Tsuda M, Sekine T, Takeda M, Cha SH, Kanai Y, Kimura M, Endou H: Transport of ochratoxin A by renal multispecific organic anion transporter 1. J Pharmacol Exp Ther. 1999 Jun;289(3):1301-5. Pubmed

2. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

References:

  1. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. Pubmed
  2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  3. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed

3. Solute carrier family 22 member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 11 Q9NSA0 Details

References:

  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H: Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta. 2002 Jun 12;1590(1-3):64-75. Pubmed
  2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11