Pentoxifylline

Synonyms :
Oxpentifylline, Pentoxifilina, Pentoxifyllin, Pentoxifylline, Pentoxifyllinum, Pentoxil, Trental

Status : approved

Category

Platelet Aggregation Inhibitors

Therapeutic Classification

PERIPHERAL VASODILATORS

CARDIOVASCULAR SYSTEM
PERIPHERAL VASODILATORS
PERIPHERAL VASODILATORS
Phosphodiesterase Inhibitors

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]

Used

For the treatment of patients with intermittent lameness or immobility arising from chronic occlusive arterial disease of the limbs.

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.

Dosage

Form Route Strength
Tablet, extended release oral 400 mg
Tablet, film coated, extended release oral 400 mg
Tablet (extended-release) oral 400 mg

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.

Toxic Effect

LD50=1385 mg/kg(orally in mice)

Half Life

0.4-0.8 hours

Protein Binding

70%

Elimination Route

Excretion is almost totally urinary; the main biotransformation product is Metabolite V. Essentially no parent drug is found in the urine.

Chemical Classification

This compound belongs to the class of organic compounds known as alkaloids and derivatives. These are naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine, and phosphorus.

Alkaloids and derivatives

Organic compounds

Alkaloids and derivatives

Chemical Name

Oxpentifylline

Brands

name Dosage form Country
Nu-pentoxifylline-sr 400 mg tablet (extended-release) Canada
Pentoxifylline tablet, film coated, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, film coated, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, film coated, extended release US
Pentoxifylline tablet, film coated, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, film coated, extended release US
Pentoxifylline tablet, film coated, extended release US
Pentoxifylline tablet, film coated, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, film coated, extended release US
Pentoxifylline tablet, film coated, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, film coated, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline tablet, extended release US
Pentoxifylline SR tablet (extended-release) Canada
Ratio-pentoxifylline tablet (extended-release) Canada
Trental tablet (extended-release) Canada
Trental Srt 400mg tablet (extended-release) Canada
Trental Tab 400mg tablet (extended-release) Canada

Drug Drug Interactions

  •  Abciximab  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Acebutolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Acenocoumarol  : May enhance the anticoagulant effect of Vitamin K Antagonists.
  •  Acetylsalicylic acid  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Aliskiren  : May enhance the hypotensive effect of Antihypertensives.
  •  Amiloride  : May enhance the hypotensive effect of Antihypertensives.
  •  Aminophylline  : May increase the serum concentration of Theophylline Derivatives.
  •  Amlodipine  : May enhance the hypotensive effect of Antihypertensives.
  •  Anagrelide  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Atenolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Azilsartan medoxomil  : May enhance the hypotensive effect of Antihypertensives.
  •  Benazepril  : May enhance the hypotensive effect of Antihypertensives.
  •  Bendroflumethiazide  : May enhance the hypotensive effect of Antihypertensives.
  •  Betaxolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Bisoprolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Bumetanide  : May enhance the hypotensive effect of Antihypertensives.
  •  Candesartan  : May enhance the hypotensive effect of Antihypertensives.
  •  Cangrelor  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Captopril  : May enhance the hypotensive effect of Antihypertensives.
  •  Carvedilol  : May enhance the hypotensive effect of Antihypertensives.
  •  Chlorothiazide  : May enhance the hypotensive effect of Antihypertensives.
  •  Chlorthalidone  : May enhance the hypotensive effect of Antihypertensives.
  •  Cilazapril  : May enhance the hypotensive effect of Antihypertensives.
  •  Cilostazol  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Cimetidine  : May increase the serum concentration of Pentoxifylline.
  •  Ciprofloxacin  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pentoxifylline.
  •  Citalopram  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Clevidipine  : May enhance the hypotensive effect of Antihypertensives.
  •  Clonidine  : May enhance the hypotensive effect of Antihypertensives.
  •  Clopidogrel  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Dalteparin  : May enhance the anticoagulant effect of Heparin (Low Molecular Weight).
  •  Desvenlafaxine  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Diclofenac  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Diflunisal  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Dihydrocodeine  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Diltiazem  : May enhance the hypotensive effect of Antihypertensives.
  •  Dipyridamole  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Doxazosin  : May enhance the hypotensive effect of Antihypertensives.
  •  Duloxetine  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Enalapril  : May enhance the hypotensive effect of Antihypertensives.
  •  Enoxaparin  : May enhance the anticoagulant effect of Heparin (Low Molecular Weight).
  •  Eplerenone  : May enhance the hypotensive effect of Antihypertensives.
  •  Eprosartan  : May enhance the hypotensive effect of Antihypertensives.
  •  Eptifibatide  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Escitalopram  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Esmolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Ethacrynic acid  : May enhance the hypotensive effect of Antihypertensives.
  •  Etodolac  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Felodipine  : May enhance the hypotensive effect of Antihypertensives.
  •  Fenoprofen  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Floctafenine  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Fluoxetine  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Flurbiprofen  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Fluvoxamine  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Fluvoxamine  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pentoxifylline.
  •  Fosinopril  : May enhance the hypotensive effect of Antihypertensives.
  •  Furosemide  : May enhance the hypotensive effect of Antihypertensives.
  •  Guanfacine  : May enhance the hypotensive effect of Antihypertensives.
  •  Heparin  : Pentoxifylline may enhance the anticoagulant effect of Heparin.
  •  Hydralazine  : May enhance the hypotensive effect of Antihypertensives.
  •  Hydrochlorothiazide  : May enhance the hypotensive effect of Antihypertensives.
  •  Ibuprofen  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Indapamide  : May enhance the hypotensive effect of Antihypertensives.
  •  Indomethacin  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Irbesartan  : May enhance the hypotensive effect of Antihypertensives.
  •  Isradipine  : May enhance the hypotensive effect of Antihypertensives.
  •  Ketoprofen  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Ketorolac  : Ketorolac (Systemic) may enhance the adverse/toxic effect of Pentoxifylline. Specifically, the risk of bleeding may be increased with this combination.
  •  Labetalol  : May enhance the hypotensive effect of Antihypertensives.
  •  Levomilnacipran  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Lisinopril  : May enhance the hypotensive effect of Antihypertensives.
  •  Losartan  : May enhance the hypotensive effect of Antihypertensives.
  •  Mannitol  : May enhance the hypotensive effect of Antihypertensives.
  •  Mecamylamine  : May enhance the hypotensive effect of Antihypertensives.
  •  Mefenamic acid  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Meloxicam  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Methoxsalen  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pentoxifylline.
  •  Methyclothiazide  : May enhance the hypotensive effect of Antihypertensives.
  •  Methyldopa  : May enhance the hypotensive effect of Antihypertensives.
  •  Metolazone  : May enhance the hypotensive effect of Antihypertensives.
  •  Metoprolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Milnacipran  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Minoxidil  : May enhance the hypotensive effect of Antihypertensives.
  •  Moexipril  : May enhance the hypotensive effect of Antihypertensives.
  •  Nabumetone  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Nadolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Nadroparin  : May enhance the anticoagulant effect of Heparin (Low Molecular Weight).
  •  Naproxen  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Nebivolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Nicardipine  : May enhance the hypotensive effect of Antihypertensives.
  •  Nifedipine  : May enhance the hypotensive effect of Antihypertensives.
  •  Nimodipine  : May enhance the hypotensive effect of Antihypertensives.
  •  Nisoldipine  : May enhance the hypotensive effect of Antihypertensives.
  •  Nitroprusside  : May enhance the hypotensive effect of Antihypertensives.
  •  Ofloxacin  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pentoxifylline.
  •  Olmesartan  : May enhance the hypotensive effect of Antihypertensives.
  •  Oxaprozin  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Paroxetine  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Penbutolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Perindopril  : May enhance the hypotensive effect of Antihypertensives.
  •  Phenoxybenzamine  : May enhance the hypotensive effect of Antihypertensives.
  •  Phentolamine  : May enhance the hypotensive effect of Antihypertensives.
  •  Pindolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Piroxicam  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Prasugrel  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Prazosin  : May enhance the hypotensive effect of Antihypertensives.
  •  Primaquine  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pentoxifylline.
  •  Propranolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Quinapril  : May enhance the hypotensive effect of Antihypertensives.
  •  Ramipril  : May enhance the hypotensive effect of Antihypertensives.
  •  Reserpine  : May enhance the hypotensive effect of Antihypertensives.
  •  Sertraline  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Sotalol  : May enhance the hypotensive effect of Antihypertensives.
  •  Spironolactone  : May enhance the hypotensive effect of Antihypertensives.
  •  Stiripentol  : CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pentoxifylline.
  •  Sulindac  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Telmisartan  : May enhance the hypotensive effect of Antihypertensives.
  •  Terazosin  : May enhance the hypotensive effect of Antihypertensives.
  •  Theophylline  : May increase the serum concentration of Theophylline Derivatives.
  •  Tiaprofenic acid  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Ticagrelor  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Ticlopidine  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Timolol  : May enhance the hypotensive effect of Antihypertensives.
  •  Tinzaparin  : May enhance the anticoagulant effect of Heparin (Low Molecular Weight).
  •  Tirofiban  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Tizanidine  : CYP1A2 Inhibitors (Weak) may increase the serum concentration of Tizanidine.
  •  Tolmetin  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Torasemide  : May enhance the hypotensive effect of Antihypertensives.
  •  Trandolapril  : May enhance the hypotensive effect of Antihypertensives.
  •  Triamterene  : May enhance the hypotensive effect of Antihypertensives.
  •  Valsartan  : May enhance the hypotensive effect of Antihypertensives.
  •  Venlafaxine  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Verapamil  : May enhance the hypotensive effect of Antihypertensives.
  •  Vilazodone  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Vorapaxar  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Vortioxetine  : May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
  •  Warfarin  : May enhance the anticoagulant effect of Vitamin K Antagonists.

Food Interactions

  • Take with food to reduce irritation. Limit caffeine intake.

Calculated Property

kind Value Source
logP 0.08 ALOGPS
logS -1.7 ALOGPS
Water Solubility 5.17e+00 g/l ALOGPS
logP 0.23 ChemAxon
IUPAC Name 3,7-dimethyl-1-(5-oxohexyl)-2,3,6,7-tetrahydro-1H-purine-2,6-dione ChemAxon
Traditional IUPAC Name pentoxifylline ChemAxon
Molecular Weight 278.307 ChemAxon
Monoisotopic Weight 278.137890462 ChemAxon
SMILES CN1C=NC2=C1C(=O)N(CCCCC(C)=O)C(=O)N2C ChemAxon
Molecular Formula C13H18N4O3 ChemAxon
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 ChemAxon
InChIKey InChIKey=BYPFEZZEUUWMEJ-UHFFFAOYSA-N ChemAxon
Polar Surface Area (PSA) 75.51 ChemAxon
Refractivity 73.52 ChemAxon
Polarizability 29.27 ChemAxon
Rotatable Bond Count 5 ChemAxon
H Bond Acceptor Count 4 ChemAxon
H Bond Donor Count 0 ChemAxon
pKa (strongest acidic) 19.64 ChemAxon
pKa (strongest basic) -0.93 ChemAxon
Physiological Charge 0 ChemAxon
Number of Rings 2 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • cAMP-specific 3′,5′-cyclic phosphodiesterase 4B : in Human
  • Adenosine receptor A1 : in Human
  • cGMP-specific 3′,5′-cyclic phosphodiesterase : in Human
  • cAMP-specific 3′,5′-cyclic phosphodiesterase 4A : in Human
  • Adenosine receptor A2a : in Human
  • 5′-nucleotidase : in Human