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Identification
NamePhenylbutazone
Accession NumberDB00812  (APRD00409, DB08343)
Typesmall molecule
Groupsapproved
Description

A drug that has anti-inflammatory, antipyretic, and analgesic activities. It is especially effective in the treatment of ankylosing spondylitis. It also is useful in rheumatoid arthritis and Reiter's syndrome (investigational indication). Although phenylbutazone is effective in gouty arthritis, risk/benefit considerations indicate that this drug should not be employed for this disease. (From AMA Drug Evaluations Annual, 1994, p1822)

Structure
Thumb
Synonyms
SynonymLanguageCode
3,5-Dioxo-1,2-diphenyl-4-n-butylpyrazolidineNot AvailableNot Available
4-BUTYL-1,2-diphenyl-pyrazolidine-3,5-dioneNot AvailableNot Available
4-n-Butyl-1,2-diphenyl-3,5-pyrazolidinedioneNot AvailableNot Available
FenilbutazonaNot AvailableNot Available
PhenbutazoneNot AvailableNot Available
PhenylbutazonNot AvailableNot Available
PhenylbutazoneNot AvailableNot Available
PhenylbutazonumNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AzolidNot Available
Brand mixtures
Brand NameIngredients
Alka Phenyl TabAluminum Hydroxide + Magnesium Trisilicate + Phenylbutazone
Alka Phenylbutazone TabAluminum Hydroxide + Magnesium Trisilicate + Phenylbutazone
Phenylone Plus TabAluminum Hydroxide + Magnesium Trisilicate + Phenylbutazone
Categories
CAS number50-33-9
WeightAverage: 308.3743
Monoisotopic: 308.152477894
Chemical FormulaC19H20N2O2
InChI KeyVYMDGNCVAMGZFE-UHFFFAOYSA-N
InChI
InChI=1S/C19H20N2O2/c1-2-3-14-17-18(22)20(15-10-6-4-7-11-15)21(19(17)23)16-12-8-5-9-13-16/h4-13,17H,2-3,14H2,1H3
IUPAC Name
4-butyl-1,2-diphenylpyrazolidine-3,5-dione
SMILES
CCCCC1C(=O)N(N(C1=O)C1=CC=CC=C1)C1=CC=CC=C1
Mass Specshow(9.03 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassNot Available
Direct parentBenzene and Substituted Derivatives
Alternative parentsPyrazolidinones; Carboxylic Acid Hydrazides; Polyamines; Carboxylic Acid Amides; Hydrazines and Derivatives
Substituentspyrazolidine; carboxylic acid hydrazide; carboxamide group; carboxylic acid derivative; polyamine; hydrazine derivative; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzene and substituted derivatives. These are aromatic compounds containing at least one benzene ring.
Pharmacology
IndicationFor the treatment of backache and ankylosing spondylitis
PharmacodynamicsPhenylbutazone is a synthetic, pyrazolone derivative. It is a nonhormonal anti-inflammatory, antipyretic compound useful in the management of inflammatory conditions. The apparent analgesic effect is probably related mainly to the compound's anti-inflammatory properties and arise from its ability to reduce production of prostaglandin H and prostacyclin. Prostaglandins act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostacylcin causes vascular constriction platelet disaggregation
Mechanism of actionPhenylbutazone binds to and inactivates prostaglandin H synthase and prostacyclin synthase through peroxide (H2O2) mediated deactivation. The reduced production of prostaglandin leads to reduced inflammation of the surrounding tissues.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityOral, LD50 = 238 mg/kg (mouse); Oral, LD50 = 781 mg/kg (rabbit); Oral, LD50 = 245 mg/kg (rat); Oral, LD50 = 375 mg/kg (rat)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Phenylbutazone Action PathwayDrug actionSMP00701
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9931
Caco-2 permeable + 0.6185
P-glycoprotein substrate Non-substrate 0.7632
P-glycoprotein inhibitor I Non-inhibitor 0.5423
P-glycoprotein inhibitor II Inhibitor 0.5596
Renal organic cation transporter Non-inhibitor 0.866
CYP450 2C9 substrate Non-substrate 0.6378
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.5439
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Inhibitor 0.5752
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.5968
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5233
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.7995
Biodegradation Not ready biodegradable 0.9881
Rat acute toxicity 2.7753 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9469
hERG inhibition (predictor II) Non-inhibitor 0.892
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Novartis pharmaceuticals corp
  • Ivax pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Sandoz inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Phenylbutazone powder1.16USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point105 °CPhysProp
water solubility47.5 mg/L (at 30 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.16SANGSTER (1994)
logS-3.81ADME Research, USCD
pKa4.5SERJEANT,EP & DEMPSEY,B (1979)
Predicted Properties
PropertyValueSource
water solubility1.44e-01 g/lALOGPS
logP2.81ALOGPS
logP4.14ChemAxon
logS-3.3ALOGPS
pKa (strongest acidic)5.13ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area40.62ChemAxon
rotatable bond count5ChemAxon
refractivity88.76ChemAxon
polarizability34.15ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Dieter Rahtz, Henning Koch, Erich Gerhards, “Hydroxy phenylbutazone derivatives and their preparation.” U.S. Patent US3968219, issued January, 1971.

US3968219
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00510
KEGG CompoundC07440
PubChem Compound4781
PubChem Substance46507038
ChemSpider4617
ChEBI48574
ChEMBLCHEMBL101
Therapeutic Targets DatabaseDAP000974
PharmGKBPA450932
HETP1Z
Drug Product Database596701
WikipediaPhenylbutazone
ATC CodesM01AA01M02AA01
AHFS Codes
  • 28:08.04.92
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.1 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolThe NSAID, phenylbutazone, may increase the anticoagulant effect of acenocoumarol.
AcetohexamidePhenylbutazone may increase the effect of acetohexamide.
AnisindioneThe NSAID, phenylbutazone, may increase the anticoagulant effect of anisindione.
ChlorpropamidePhenylbutazone increases the effect of the hypoglycemic agent
DicoumarolThe NSAID, phenylbutazone, may increase the anticoagulant effect of dicumarol.
EthotoinThe NSAID, phenylbutazone, may increase the hydantoin effect of ethotoin.
FosphenytoinThe NSAID, phenylbutazone, may increase the hydantoin effect of fosphenytoin.
GliclazidePhenylbutazone increases the effect of the hypoglycemic agent
GlipizidePhenylbutazone increases the effect of the hypoglycemic agent
GlisoxepidePhenylbutazone increases the effect of the hypoglycemic agent
GlyburidePhenylbutazone increases the effect of the hypoglycemic agent
GlycodiazinePhenylbutazone increases the effect of the hypoglycemic agent
LithiumThe NSAID, phenylbutazone, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
MephenytoinThe NSAID, phenylbutazone, may increase the hydantoin effect of mephenytoin.
MethotrexateThe NSAID, phenylbutazone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
PhenytoinThe NSAID, phenylbutazone, may increase the therapeutic and adverse effects of phenytoin.
TolazamidePhenylbutazone increases the effect of the hypoglycemic agent
TolbutamidePhenylbutazone increases the effect of the hypoglycemic agent
WarfarinThe NSAID, phenylbutazone, may increase the anticoagulant effect of warfarin.
Food Interactions
  • Take with food to reduce irritation. 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. Arifah AK, Lees P: Pharmacodynamics and pharmacokinetics of phenylbutazone in calves. J Vet Pharmacol Ther. 2002 Aug;25(4):299-309. Pubmed
  2. Takada Y, Bhardwaj A, Potdar P, Aggarwal BB: Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene. 2004 Dec 9;23(57):9247-58. Pubmed
  3. Beretta C, Garavaglia G, Cavalli M: COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. Pharmacol Res. 2005 Oct;52(4):302-6. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostacyclin synthase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostacyclin synthase Q16647 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Reed GA, Griffin IO, Eling TE: Inactivation of prostaglandin H synthase and prostacyclin synthase by phenylbutazone. Requirement for peroxidative metabolism. Mol Pharmacol. 1985 Jan;27(1):109-14. Pubmed
  4. Marnett LJ, Siedlik PH, Ochs RC, Pagels WR, Das M, Honn KV, Warnock RH, Tainer BE, Eling TE: Mechanism of the stimulation of prostaglandin H synthase and prostacyclin synthase by the antithrombotic and antimetastatic agent, nafazatrom. Mol Pharmacol. 1984 Sep;26(2):328-35. Pubmed
  5. Tobin T, Chay S, Kamerling S, Woods WE, Weckman TJ, Blake JW, Lees P: Phenylbutazone in the horse: a review. J Vet Pharmacol Ther. 1986 Mar;9(1):1-25. Pubmed

3. 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. Zitova A, Hynes J, Kollar J, Borisov SM, Klimant I, Papkovsky DB: Analysis of activity and inhibition of oxygen-dependent enzymes by optical respirometry on the LightCycler system. Anal Biochem. 2010 Feb 15;397(2):144-51. Epub 2009 Oct 20. Pubmed
  2. Beretta C, Garavaglia G, Cavalli M: COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. Pharmacol Res. 2005 Oct;52(4):302-6. Pubmed
  3. Morton AJ, Campbell NB, Gayle JM, Redding WR, Blikslager AT: Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis. Res Vet Sci. 2005 Apr;78(2):189-92. 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. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 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

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. 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
  2. Uwai Y, Saito H, Inui K: Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter. Eur J Pharmacol. 2000 Dec 1;409(1):31-6. Pubmed
  3. 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

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. 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. 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. 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 17:12