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Identification
NamePentoxifylline
Accession NumberDB00806  (APRD00121)
Typesmall molecule
Groupsapproved, investigational
Description

A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
OxpentifyllineNot AvailableIS
PentoxifilinaSpanishINN
PentoxifyllinGermanINN
PentoxifyllineFrenchINN
PentoxifyllinumLatinINN
SaltsNot Available
Brand names
NameCompany
AgapurinZentiva
Agapurin SRZentiva
An Ruo NingNanjing Yaoda Bio-Pharmaceutical
AngiopentHelcor
Ao Le NiC & O Pharmaceuticals
Ao Nuo HongAosaiKang Pharmaceutical
AotongTreeful Pharmaceutical
AzupentatNot Available
BehrifilSanofi-Aventis
Bo Shu TeJisheng Pharmaceutical
ClaudicatNycomed
DurapentalMylan dura
ElorganSanofi Aventis
EndopentoksasEndokriniai
PentilinKrka
Pentilin RetardKrka
PentofluxBouchara-Recordati
PentofyllinSopharma
PentoksifilinPanfarma
PentolabLamsa
Pentomerratiopharm
PentoxilUpsher-Smith
RentylinAmdipharm
TorentalSanofi-Aventis
TrentalSanofi-Aventis
Trentilin RetardSanta-Farma
Brand mixtures
Brand NameIngredients
Tri-PlenPentoxifylline and Felodipine
Categories
CAS number6493-05-6
WeightAverage: 278.307
Monoisotopic: 278.137890462
Chemical FormulaC13H18N4O3
InChI KeyBYPFEZZEUUWMEJ-UHFFFAOYSA-N
InChI
InChI=1S/C13H18N4O3/c1-9(18)6-4-5-7-17-12(19)10-11(14-8-15(10)2)16(3)13(17)20/h8H,4-7H2,1-3H3
IUPAC Name
3,7-dimethyl-1-(5-oxohexyl)-2,3,6,7-tetrahydro-1H-purine-2,6-dione
SMILES
CN1C=NC2=C1C(=O)N(CCCCC(C)=O)C(=O)N2C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassImidazopyrimidines
SubclassPurines and Purine Derivatives
Direct parentXanthines
Alternative parentsPurinones; Pyrimidones; N-substituted Imidazoles; Ketones; Polyamines; Enolates
Substituentspyrimidone; pyrimidine; n-substituted imidazole; azole; imidazole; ketone; enolate; polyamine; organonitrogen compound; amine; carbonyl group
Classification descriptionThis compound belongs to the xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
Pharmacology
IndicationFor the treatment of patients with intermittent lameness or immobility arising from chronic occlusive arterial disease of the limbs.
PharmacodynamicsPentoxifylline, a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine, is used in the treatment of peripheral vascular diseases and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy.
Mechanism of actionPentoxifylline inhibits erythrocyte phosphodiesterase, resulting in an increase in erythrocyte cAMP activity. Subsequently, the erythrocyte membrane becomes more resistant to deformity. Along with erythrocyte activity, pentoxifylline also decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity. It is also a non selective adenosine receptor antagonist.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding70%
Metabolism
Route of eliminationExcretion is almost totally urinary; the main biotransformation product is Metabolite V. Essentially no parent drug is found in the urine.
Half life0.4-0.8 hours
ClearanceNot Available
ToxicityLD50=1385 mg/kg(orally in mice)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
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 + 0.9851
Caco-2 permeable - 0.5056
P-glycoprotein substrate Substrate 0.595
P-glycoprotein inhibitor I Non-inhibitor 0.6905
P-glycoprotein inhibitor II Inhibitor 0.7157
Renal organic cation transporter Non-inhibitor 0.7023
CYP450 2C9 substrate Non-substrate 0.7897
CYP450 2D6 substrate Non-substrate 0.9117
CYP450 3A4 substrate Substrate 0.6511
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.9518
CYP450 2D6 substrate Non-inhibitor 0.943
CYP450 2C19 substrate Non-inhibitor 0.9313
CYP450 3A4 substrate Non-inhibitor 0.9827
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.901
Ames test Non AMES toxic 0.7131
Carcinogenicity Non-carcinogens 0.8965
Biodegradation Not ready biodegradable 0.7457
Rat acute toxicity 2.4070 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.6463
hERG inhibition (predictor II) Non-inhibitor 0.8734
Pharmacoeconomics
Manufacturers
  • Actavis elizabeth llc
  • Apotex inc
  • Biovail laboratories inc
  • Heritage pharmaceuticals inc
  • Impax laboratories inc
  • Mylan pharmaceuticals inc
  • Pliva inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Upsher smith laboratories inc
  • Sanofi aventis us llc
Packagers
Dosage forms
FormRouteStrength
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
TRENtal 400 mg Controlled Release Tabs1.4USDtab
Trental er 400 mg tablet1.27USDtablet
Pentoxifylline powder0.91USDg
Trental 400 mg Sustained-Release Tablet0.88USDtablet
Pentoxifylline 400 mg tablet sa0.71USDtablet
Pentoxifylline CR 400 mg Controlled Release Tabs0.62USDtab
Pentoxil 400 mg Controlled Release Tabs0.62USDtab
Pentoxil er 400 mg tablet0.62USDtablet
Pentoxifylline er 400 mg tablet0.6USDtablet
Apo-Pentoxifylline Sr 400 mg Sustained-Release Tablet0.4USDtablet
Nu-Pentoxifylline-Sr 400 mg Sustained-Release Tablet0.4USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point105 °CNot Available
water solubility7.7E+004 mg/L (at 25 °C)MERCK INDEX (1996)
logP0.29BIOBYTE (1995)
Predicted Properties
PropertyValueSource
water solubility5.17e+00 g/lALOGPS
logP0.08ALOGPS
logP0.23ChemAxon
logS-1.7ALOGPS
pKa (strongest acidic)19.64ChemAxon
pKa (strongest basic)-0.93ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count0ChemAxon
polar surface area75.51ChemAxon
rotatable bond count5ChemAxon
refractivity73.52ChemAxon
polarizability29.27ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. : European Pentoxifylline Multi-Infarct Dementia Study. Eur Neurol. 1996;36(5):315-21. Pubmed
External Links
ResourceLink
KEGG DrugD00501
KEGG CompoundC07424
PubChem Compound4740
PubChem Substance46505940
ChemSpider4578
BindingDB10850
Therapeutic Targets DatabaseDAP000048
PharmGKBPA450864
Drug Product Database1968432
RxListhttp://www.rxlist.com/cgi/generic/pentox.htm
Drugs.comhttp://www.drugs.com/cdi/pentoxifylline.html
WikipediaPentoxifylline
ATC CodesC04AD03
AHFS Codes
  • 20:24.00
PDB EntriesNot Available
FDA labelshow(51.7 KB)
MSDSshow(73.9 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolPentoxifylline may increase the anticoagulant effect of acenocoumarol.
AminophyllinePentoxifylline may increase the effect and toxicity of aminophylline.
AnisindionePentoxifylline may increase the anticoagulant effect of anisindione.
DicoumarolPentoxifylline may increase the anticoagulant effect of dicumarol.
DyphyllinePentoxifylline increases the effect and toxicity of theophylline
Insulin LisproConcomitant therapy with drugs that may increase the blood-glucose-lowering effect of insulin lispro and thus the chance of hypoglycemia should be monitored closely.
OxtriphyllinePentoxifylline increases the effect and toxicity of theophylline
TheophyllinePentoxifylline increases the effect and toxicity of theophylline
WarfarinPentoxifylline may increase the anticoagulant effect of warfarin.
Food Interactions
  • Take with food to reduce irritation. Limit caffeine intake.

Targets

1. cAMP-specific 3',5'-cyclic phosphodiesterase 4B

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
cAMP-specific 3',5'-cyclic phosphodiesterase 4B Q07343 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

2. Adenosine receptor A1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Adenosine receptor A1 P30542 Details

References:

  1. Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. Pubmed

3. cGMP-specific 3',5'-cyclic phosphodiesterase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
cGMP-specific 3',5'-cyclic phosphodiesterase O76074 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. cAMP-specific 3',5'-cyclic phosphodiesterase 4A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
cAMP-specific 3',5'-cyclic phosphodiesterase 4A P27815 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

5. Adenosine receptor A2a

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Adenosine receptor A2a P29274 Details

References:

  1. Kreth S, Ledderose C, Luchting B, Weis F, Thiel M: Immunomodulatory properties of pentoxifylline are mediated via adenosine-dependent pathways. Shock. 2010 Jul;34(1):10-6. Pubmed

6. 5'-nucleotidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
5'-nucleotidase P21589 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Ustunsoy H, Sivrikoz MC, Tarakcioglu M, Bakir K, Guldur E, Celkan MA: The effects of pentoxifylline on the myocardial inflammation and ischemia-reperfusion injury during cardiopulmonary bypass. J Card Surg. 2006 Jan-Feb;21(1):57-61. Pubmed

Enzymes

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 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

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Drug created on June 13, 2005 07:24 / Updated on November 14, 2013 11:35