Pentoxifylline

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Pentoxifylline
Systematic (IUPAC) name
3,7-Dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione
Clinical data
Trade namesTrental
AHFS/Drugs.commonograph
MedlinePlusa685027
Pregnancy cat.C (US)
Legal status ?
RoutesOral
Pharmacokinetic data
BioavailabilityNear 100% for oral dosing
MetabolismHepatic and via erythrocytes
Half-life0.4 - 0.8 hours (1 - 1.6 hours for active metabolite)
ExcretionMainly urine (<4% feces)
Identifiers
CAS number6493-05-6 YesY
ATC codeC04AD03
PubChemCID 4740
DrugBankDB00806
ChemSpider4578 YesY
UNIISD6QCT3TSU YesY
KEGGD00501 YesY
ChEMBLCHEMBL628 YesY
Chemical data
FormulaC13H18N4O3 
Mol. mass278.31 g/mol
 YesY (what is this?)  (verify)
 
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Pentoxifylline
Systematic (IUPAC) name
3,7-Dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione
Clinical data
Trade namesTrental
AHFS/Drugs.commonograph
MedlinePlusa685027
Pregnancy cat.C (US)
Legal status ?
RoutesOral
Pharmacokinetic data
BioavailabilityNear 100% for oral dosing
MetabolismHepatic and via erythrocytes
Half-life0.4 - 0.8 hours (1 - 1.6 hours for active metabolite)
ExcretionMainly urine (<4% feces)
Identifiers
CAS number6493-05-6 YesY
ATC codeC04AD03
PubChemCID 4740
DrugBankDB00806
ChemSpider4578 YesY
UNIISD6QCT3TSU YesY
KEGGD00501 YesY
ChEMBLCHEMBL628 YesY
Chemical data
FormulaC13H18N4O3 
Mol. mass278.31 g/mol
 YesY (what is this?)  (verify)

Pentoxifylline (INN) is a drug commonly sold by Aventis under the brand name Trental. Its chemical name is 1-(5-oxohexyl)-3, 7-dimethylxanthine. Pentoxifylline is a xanthine derivative. Other brand names include Pentox, Pentoxil, and Flexital.

Uses[edit]

It is used to treat intermittent claudication resulting from obstructed arteries in the limbs,[1] and vascular dementia.[2]

Pentoxifylline improves blood flow through peripheral blood vessels and therefore helps with blood circulation in the arms and legs (e.g. intermittent claudication), and the brain (hence its use in vascular dementia).[citation needed]

The drug is gaining acceptance for conservative treatment of Peyronie's disease and neuropathic injuries. It also helps prevent strokes and can be used in managing sickle cell disease.

Pentoxifylline has also been used to treat nausea and headaches in the mountains (altitude sickness), and has been shown to reduce mortality in acute alcoholic and non-alcoholic steatohepatitis, presumably through its ability to inhibit TNF. Pentoxifylline's anti-TNF properties indicates it for treatment of alcoholic liver disease.

A study demonstrated the possible use of pentoxifylline administered in conjunction with vitamin E for reducing the extent of fibrotic lesions induced by radiation therapy for breast cancer,[3] as well as treating radiation and bisphosphonate necrosis of the jaw.

IV or oral pretreatment with pentoxifylline has been attempted for the treatment of cytokine release syndrome but it does not prevent symptoms in most studies.

Pentoxifillyine is also being investigated for the causative treatment of endometriosis.[4]

Pentoxifylline is also used in the treatment of venous disease.[5]

It can also be used to increase sperm motility when viable sperm are immotile and are being used in intracytoplasmic sperm injection (ICSI).

Mechanism[edit]

Like other methylated xanthine derivatives, pentoxifylline is a competitive nonselective phosphodiesterase inhibitor [6] which raises intracellular cAMP, activates PKA, inhibits TNF [7][8] and leukotriene [9] synthesis, and reduces inflammation and innate immunity.[9]

In addition, pentoxifylline improves red blood cell deformability (known as a hemorrheologic effect), reduces blood viscosity and decreases the potential for platelet aggregation and thrombus formation.[10]

Pentoxifylline is also an antagonist at adenosine 2 receptors.[11]

Drug interaction[edit]

Co-administration of pentoxifylline and sodium thiopental may cause death by acute pulmonary edema in rats.[12]

This drug is passed into the breast milk. Animal studies have shown no evidence of teratogenicity at high doses.

Brand names[edit]

See also[edit]

References[edit]

  1. ^ Salhiyyah, Kareem; Senanayake, Eshan; Abdel-Hadi, Mohammed; Booth, Andrew; Michaels, Jonathan A (2012 Jan 18). "Pentoxifylline for intermittent claudication". In Salhiyyah, Kareem. Cochrane Database Syst Rev 1 (1): CD005262. doi:10.1002/14651858.CD005262.pub2. PMID 22258961. 
  2. ^ "European Pentoxifylline Multi-Infarct Dementia Study". European neurology 36 (5): 315–21. 1996. doi:10.1159/000117279. PMID 8864715. 
  3. ^ Delanian, S; Porcher, R; Rudant, J; Lefaix, JL (2005). "Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis,". J Clin Oncol 23 (34): 8570–8579. doi:10.1200/JCO.2005.02.4729. PMID 16260695. 
  4. ^ Tulandi, Togas; Redwine, David B (2003-12-09). Endometriosis: Advances and controversies. ISBN 978-0-8247-4777-0. 
  5. ^ "The Use of Pentoxifylline in Venous Disease". Venous Review 4 (3). 2011-11-07. 
  6. ^ Essayan DM. (2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671–80. doi:10.1067/mai.2001.119555. PMID 11692087. 
  7. ^ Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R. (2008). "Insights into the Regulation of TNF-α Production in Human Mononuclear Cells: The Effects of Non-Specific Phosphodiesterase Inhibition". Clinics (Sao Paulo). 63 (3): 321–8. doi:10.1590/S1807-59322008000300006. PMC 2664230. PMID 18568240. 
  8. ^ Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (February 1999). "Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages". Am. J. Respir. Crit. Care Med. 159 (2): 508–11. doi:10.1164/ajrccm.159.2.9804085. PMID 9927365. 
  9. ^ a b Peters-Golden M, Canetti C, Mancuso P, Coffey MJ. (2005). "Leukotrienes: underappreciated mediators of innate immune responses". J Immunol. 174 (2): 589–94. PMID 15634873. 
  10. ^ Ward, A; Clissold, SP (1987). "Pentoxifylline. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy". Drugs 34 (1): 50–97. doi:10.2165/00003495-198734010-00003. PMID 3308412. 
  11. ^ Rodríguez-Morán M, Guerrero-Romero F (February 2008). "Efficacy of pentoxifylline in the management of microalbuminuria in patients with diabetes". Curr Diabetes Rev 4 (1): 55–62. doi:10.2174/157339908783502343. PMID 18220696. 
  12. ^ Pereda, J; Gómez-Cambronero, L; Alberola, A; Fabregat, G; Cerdá, M; Escobar, J; Sabater, L; García-De-La-Asunción, J; Viña, J; Sastre, J (2006). "Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats". British Journal of Pharmacology 149 (4): 450–5. doi:10.1038/sj.bjp.0706871. PMC 1978439. PMID 16953192. 

External links[edit]