Pentoxifylline
Identification
- Name
- Pentoxifylline
- Accession Number
- DB00806 (APRD00121)
- Type
- Small Molecule
- Groups
- Approved, 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
- Synonyms
- Oxpentifylline
- Pentoxifilina
- Pentoxifyllin
- Pentoxifylline
- Pentoxifyllinum
- External IDs
- BL 191 / BL-191 / C04AD03 / PTX
- Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Pentoxifylline SR Tablet, extended release 400 mg Oral Aa Pharma Inc 1997-01-14 Not applicable Canada Trental Tablet, extended release 400 mg Oral Sanofi Aventis 1996-10-23 2013-03-01 Canada Trental Tablet, film coated, extended release 400 mg/1 Oral Sanofi Aventis 1984-08-30 2013-12-31 US Trental Tablet, film coated 400 mg/1 Oral Physicians Total Care, Inc. 1984-08-30 2011-09-30 US Trental Srt 400mg Tablet, extended release 400 mg Oral Hoechst Roussel Canada Inc. 1993-12-31 1998-08-12 Canada Trental Tab 400mg Tablet, extended release 400 mg Oral Hoechst Canada Inc. 1984-12-31 1996-08-29 Canada - Generic Prescription Products
- Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Gapeam Budibac Pentoxifylline (1 g/1g) + Amantadine hydrochloride (1 g/1g) + Baclofen (1 g/1g) + Bupivacaine hydrochloride (1 g/1g) + Cyclobenzaprine hydrochloride (1 g/1g) + Diclofenac sodium (1 g/1g) + Gabapentin (1 g/1g) Kit Topical Alvix Laboratories 2014-12-05 2018-03-08 US - International/Other Brands
- Agapurin (Zentiva) / Agapurin SR (Zentiva) / An Ruo Ning (Nanjing Yaoda Bio-Pharmaceutical) / Angiopent (Helcor) / Ao Le Ni (C & O Pharmaceuticals) / Ao Nuo Hong (AosaiKang Pharmaceutical) / Aotong (Treeful Pharmaceutical) / Azupentat / Behrifil (Sanofi-Aventis) / Bo Shu Te (Jisheng Pharmaceutical) / Claudicat (Nycomed) / Durapental (Mylan dura) / Elorgan (Sanofi Aventis) / Endopentoksas (Endokriniai) / Pentilin (Krka) / Pentilin Retard (Krka) / Pentoflux (Bouchara-Recordati) / Pentofyllin (Sopharma) / Pentoksifilin (Panfarma) / Pentolab (Lamsa) / Pentomer (ratiopharm) / Pentoxil (Upsher-Smith) / Rentylin (Amdipharm) / Torental (Sanofi-Aventis) / Trental / Trentilin Retard (Santa-Farma)
- Categories
- Alkaloids
- Antioxidants
- Antiplatelet agents
- Blood Viscosity Reducer
- Cardiovascular Agents
- Cytochrome P-450 CYP1A2 Substrates
- Drugs for Obstructive Airway Diseases
- Enzyme Inhibitors
- Free Radical Scavengers
- Hematologic Activity Alteration
- Hematologic Agents
- Hemorrheologic Agents
- Peripheral Vasodilators
- Phosphodiesterase 5 Inhibitors
- Phosphodiesterase Inhibitors
- Protective Agents
- Purine Derivatives
- Purines
- Purinones
- Radiation-Protective Agents
- Theobromine
- Vasodilating Agents
- Xanthine derivatives
- UNII
- SD6QCT3TSU
- CAS number
- 6493-05-6
- Weight
- Average: 278.307
Monoisotopic: 278.137890462 - Chemical Formula
- C13H18N4O3
- InChI Key
- BYPFEZZEUUWMEJ-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
Pharmacology
- Indication
For the treatment of patients with intermittent lameness or immobility arising from chronic occlusive arterial disease of the limbs.
- Associated Conditions
- Pharmacodynamics
Pentoxifylline, 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 action
Pentoxifylline 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.
Target Actions Organism AcAMP-specific 3',5'-cyclic phosphodiesterase 4B inhibitorHumans AAdenosine receptor A1 antagonistHumans AcGMP-specific 3',5'-cyclic phosphodiesterase inhibitorHumans AcAMP-specific 3',5'-cyclic phosphodiesterase 4A inhibitorHumans AAdenosine receptor A2a antagonistHumans U5'-nucleotidase inhibitorHumans - Absorption
- Not Available
- Volume of distribution
- Not Available
- Protein binding
70%
- Metabolism
- Not Available
- Route of elimination
Excretion is almost totally urinary; the main biotransformation product is Metabolite V. Essentially no parent drug is found in the urine.
- Half life
0.4-0.8 hours
- Clearance
- Not Available
- Toxicity
LD50=1385 mg/kg(orally in mice)
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction (R)-warfarin The therapeutic efficacy of (R)-warfarin can be increased when used in combination with Pentoxifylline. (S)-Warfarin The therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Pentoxifylline. 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid Pentoxifylline may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid. 2,5-Dimethoxy-4-ethylamphetamine The risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Pentoxifylline. 2,5-Dimethoxy-4-ethylthioamphetamine The risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Pentoxifylline. 3-isobutyl-1-methyl-7H-xanthine The serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Pentoxifylline. 3,4-Methylenedioxyamphetamine The risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Pentoxifylline. 3,5-diiodothyropropionic acid The serum concentration of Pentoxifylline can be increased when it is combined with 3,5-diiodothyropropionic acid. 4-Bromo-2,5-dimethoxyamphetamine The risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Pentoxifylline. 4-hydroxycoumarin The therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Pentoxifylline. - Food Interactions
- Take with food to reduce irritation. Limit caffeine intake.
References
- General References
- Authors unspecified: European Pentoxifylline Multi-Infarct Dementia Study. Eur Neurol. 1996;36(5):315-21. [PubMed:8864715]
- External Links
- Human Metabolome Database
- HMDB0014944
- KEGG Drug
- D00501
- KEGG Compound
- C07424
- PubChem Compound
- 4740
- PubChem Substance
- 46505940
- BindingDB
- 10850
- ChEBI
- 7986
- ChEMBL
- CHEMBL628
- Therapeutic Targets Database
- DAP000048
- PharmGKB
- PA450864
- HET
- PNX
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Pentoxifylline
- ATC Codes
- C04AD03 — Pentoxifylline
- C04AD — Purine derivatives
- C04A — PERIPHERAL VASODILATORS
- C04 — PERIPHERAL VASODILATORS
- C — CARDIOVASCULAR SYSTEM
- AHFS Codes
- 20:24.00 — Hemorrheologic Agents
- PDB Entries
- 2a3c / 3arr / 3aru / 3tvx
- FDA label
- Download (51.7 KB)
- MSDS
- Download (73.9 KB)
Clinical Trials
- Clinical Trials
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
- Amerisource Health Services Corp.
- Amneal Pharmaceuticals
- Apotex Inc.
- A-S Medication Solutions LLC
- Atlantic Biologicals Corporation
- Biovail Pharmaceuticals
- Cardinal Health
- Dept Health Central Pharmacy
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Gallipot
- Golden State Medical Supply Inc.
- Heartland Repack Services LLC
- Lake Erie Medical and Surgical Supply
- Major Pharmaceuticals
- Mckesson Corp.
- Merrell Pharmaceuticals Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Nucare Pharmaceuticals Inc.
- Pharmedix
- Physicians Total Care Inc.
- Pliva Inc.
- Prepak Systems Inc.
- Remedy Repack
- Sandhills Packaging Inc.
- Sanofi-Aventis Inc.
- Southwood Pharmaceuticals
- Teva Pharmaceutical Industries Ltd.
- Torpharm Inc.
- Tya Pharmaceuticals
- UDL Laboratories
- Upsher Smith Laboratories
- Va Cmop Dallas
- Vangard Labs Inc.
- Zoetica Pharmaceutical Corp.
- Dosage forms
Form Route Strength Kit Topical Tablet, extended release Oral 400 mg/1 Tablet, film coated, extended release Oral 400 mg/1 Tablet, extended release Oral 400 mg Tablet, film coated Oral 400 mg/1 - Prices
Unit description Cost Unit TRENtal 400 mg Controlled Release Tabs 1.4USD tab Trental er 400 mg tablet 1.27USD tablet Pentoxifylline powder 0.91USD g Trental 400 mg Sustained-Release Tablet 0.88USD tablet Pentoxifylline 400 mg tablet sa 0.71USD tablet Pentoxifylline CR 400 mg Controlled Release Tabs 0.62USD tab Pentoxil 400 mg Controlled Release Tabs 0.62USD tab Pentoxil er 400 mg tablet 0.62USD tablet Pentoxifylline er 400 mg tablet 0.6USD tablet Apo-Pentoxifylline Sr 400 mg Sustained-Release Tablet 0.4USD tablet Nu-Pentoxifylline-Sr 400 mg Sustained-Release Tablet 0.4USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 105 °C Not Available water solubility 7.7E+004 mg/L (at 25 °C) MERCK INDEX (1996) logP 0.29 BIOBYTE (1995) - Predicted Properties
Property Value Source Water Solubility 5.17 mg/mL ALOGPS logP 0.08 ALOGPS logP 0.23 ChemAxon logS -1.7 ALOGPS pKa (Strongest Acidic) 19.64 ChemAxon pKa (Strongest Basic) -0.93 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 4 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 75.51 Å2 ChemAxon Rotatable Bond Count 5 ChemAxon Refractivity 73.52 m3·mol-1 ChemAxon Polarizability 29.27 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - 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 inhibitor Non-inhibitor 0.9518 CYP450 2D6 inhibitor Non-inhibitor 0.943 CYP450 2C19 inhibitor Non-inhibitor 0.9313 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-0059-1890000000-c9be2fe26b2862cba4f5 MS/MS Spectrum - , positive LC-MS/MS splash10-001r-2900000000-d54457aaede5317cef72 LC-MS/MS Spectrum - LC-ESI-QFT , positive LC-MS/MS splash10-0059-2970000000-95d1edcd63b61b13b22e
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Imidazopyrimidines
- Sub Class
- Purines and purine derivatives
- Direct Parent
- Xanthines
- Alternative Parents
- 6-oxopurines / Alkaloids and derivatives / Pyrimidones / N-substituted imidazoles / Vinylogous amides / Heteroaromatic compounds / Ureas / Lactams / Ketones / Azacyclic compounds show 4 more
- Substituents
- Xanthine / 6-oxopurine / Purinone / Alkaloid or derivatives / Pyrimidone / N-substituted imidazole / Pyrimidine / Azole / Imidazole / Heteroaromatic compound show 14 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- oxopurine (CHEBI:7986)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Metal ion binding
- Specific Function
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging f...
- Gene Name
- PDE4B
- Uniprot ID
- Q07343
- Uniprot Name
- cAMP-specific 3',5'-cyclic phosphodiesterase 4B
- Molecular Weight
- 83342.695 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
- 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:17016423]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Purine nucleoside binding
- Specific Function
- Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name
- ADORA1
- Uniprot ID
- P30542
- Uniprot Name
- Adenosine receptor A1
- Molecular Weight
- 36511.325 Da
References
- Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. [PubMed:3588607]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Metal ion binding
- Specific Function
- Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, ...
- Gene Name
- PDE5A
- Uniprot ID
- O76074
- Uniprot Name
- cGMP-specific 3',5'-cyclic phosphodiesterase
- Molecular Weight
- 99984.14 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Metal ion binding
- Specific Function
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
- Gene Name
- PDE4A
- Uniprot ID
- P27815
- Uniprot Name
- cAMP-specific 3',5'-cyclic phosphodiesterase 4A
- Molecular Weight
- 98142.155 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Identical protein binding
- Specific Function
- Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
- Gene Name
- ADORA2A
- Uniprot ID
- P29274
- Uniprot Name
- Adenosine receptor A2a
- Molecular Weight
- 44706.925 Da
References
- 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. doi: 10.1097/SHK.0b013e3181cdc3e2. [PubMed:19997047]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Nucleotide binding
- Specific Function
- Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities.
- Gene Name
- NT5E
- Uniprot ID
- P21589
- Uniprot Name
- 5'-nucleotidase
- Molecular Weight
- 63367.255 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- 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:16426349]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
- Lee SH, Slattery JT: Cytochrome P450 isozymes involved in lisofylline metabolism to pentoxifylline in human liver microsomes. Drug Metab Dispos. 1997 Dec;25(12):1354-8. [PubMed:9394024]
- Zhou SF, Yang LP, Zhou ZW, Liu YH, Chan E: Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009 Sep;11(3):481-94. doi: 10.1208/s12248-009-9127-y. Epub 2009 Jul 10. [PubMed:19590965]
Drug created on June 13, 2005 07:24 / Updated on February 18, 2019 20:23