Pentoxifylline

Pentoxifylline

Systematic (IUPAC) name
3,7-Dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione
Clinical data
Trade names	Trental
AHFS/Drugs.com	monograph
MedlinePlus	a685027
Pregnancy cat.	C(US)
Legal status	?
Routes	Oral
Pharmacokinetic data
Bioavailability	Near 100% for oral dosing
Metabolism	Hepatic and via erythrocytes
Half-life	0.4 - 0.8 hours (1 - 1.6 hours for active metabolite)
Excretion	Mainly urine (<4% feces)
Identifiers
CAS number	6493-05-6 Y
ATC code	C04AD03
PubChem	CID 4740
DrugBank	APRD00121
ChemSpider	4578 Y
UNII	SD6QCT3TSU Y
KEGG	D00501 Y
ChEMBL	CHEMBL628 Y
Chemical data
Formula	C13H18N4O3
Mol. mass	278.31
SMILES	eMolecules & PubChem
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 Y Key:BYPFEZZEUUWMEJ-UHFFFAOYSA-N Y
Y(what is this?)  (verify)

Pentoxifylline (INN) is a drug 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

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

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).

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-alpha. 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.^[2]

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.^[3]

Mechanism

Like other methylated xanthine derivatives, pentoxifylline is both a

1. competitive nonselective phosphodiesterase inhibitor ^[4] which raises intracellular cAMP, activates PKA, inhibits TNF-alpha ^[5][6] and leukotriene ^[7] synthesis, and reduces inflammation and innate immunity ^[7] and

In addition, pentoxifylline improves red blood cell deformability, reduces blood viscosity and decreases the potential for platelet aggregation and thrombus formation.^[8]

Drug interaction

Co-administration of pentoxifylline and sodium thiopental may cause death by acute pulmonary edema in rats.^[9]

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

Brand names

• Pentoxil (Upsher Smith)
• Pentoxin (Ratiopharm)
• Artal (Leiras)
• Vasonit (Lannacher)
• Pentilin (Krka (company))

References

1. ^ "European Pentoxifylline Multi-Infarct Dementia Study". European neurology 36 (5): 315–21. 1996. doi:10.1159/000117279. PMID 8864715. 
2. ^ Delanian, S; Porcher, R; Rudant, J et al.; 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. 
3. ^ Tulandi, Togas; Redwine, David B (2003-12-09). Endometriosis: Advances and controversies. ISBN 9780824747770. http://books.google.com/?id=Q9ldvHVtWCUC&lpg=PA99&dq=pentoxifylline%20endometriosis&pg=PA99#v=onepage&q=pentoxifylline%20endometriosis&f=false. 
4. ^ Essayan DM. (2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671–80. doi:10.1067/mai.2001.119555. PMID 11692087. 
5. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2664230. 
6. ^ 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. PMID 9927365. http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=9927365. 
7. ^ ^{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. http://www.jimmunol.org/cgi/content/full/174/2/589. 
8. ^ Ward, A; Clissold, SP (1987). "Pentoxifylline. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy". Drugs 34 (1): 50–97. PMID 3308412. 
9. ^ Pereda, J; Gómez-Cambronero, L; Alberola, A; Fabregat, G; Cerdá, M; Escobar, J; Sabater, L; García-De-La-Asunción, J et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1978439. 

External links

• Trental information from Aventis
• Reprinted article on veterinary use