Pentoxifylline

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Pentoxifylline
Pentoxifylline.svg
Pentoxifylline xtal 2005 ball-and-stick.png
Clinical data
Pronunciation /?p?nt?k's?f?li?n, -?n/
Trade names Many names worldwide[1]
Synonyms oxpentifylline (former AAN)[2]
AHFS/Drugs.com Monograph
MedlinePlus a685027
License data
US FDA: Pentoxifylline
Pregnancy
category
AU: B1
US: C (Risk not ruled out)
Routes of
administration By mouth
ATC code
C04AD03 (WHO)
Legal status
Legal status
AU: S4 (Prescription only)
CA: ?-only
UK: POM (Prescription only)
US: ?-only
Pharmacokinetic data
Bioavailability 10�30%[3]
Metabolism Hepatic and via erythrocytes
Biological half-life 0.4�0.8 hours (1�1.6 hours for active metabolite)[3]
Excretion Urine (95%), faeces (<4%)[3]
Identifiers
IUPAC name[show]
CAS Number
6493-05-6 Yes
PubChem CID
4740
IUPHAR/BPS
7095
DrugBank
DB00806 Yes
ChemSpider
4578 Yes
UNII
SD6QCT3TSU
KEGG
D00501 Yes
ChEMBL
CHEMBL628 Yes
ECHA InfoCard 100.026.704 Edit this at Wikidata
Chemical and physical data
Formula C13H18N4O3
Molar mass 278.31 g/mol
3D model (JSmol)
Interactive image
SMILES[show]
InChI[show]
(verify)
Pentoxifylline, also known as oxpentifylline, is a xanthine derivative used as a
drug to treat muscle pain in people with peripheral artery disease.[4] It is
generic and sold under many brand names worldwide.[1]

Contents
1 Medical uses
2 Adverse effects
3 Mechanism
4 Effect on seizure
5 Research
6 See also
7 References
8 External links
Medical uses
Its primary use in medicine is to reduce pain, cramping, numbness, or weakness in
the arms or legs which occurs due to intermittent claudication, a form of muscle
pain resulting from peripheral artery diseases.[4] This is its only FDA, MHRA and
TGA-labelled indication.[2][5][6] However, pentoxifylline is also recommended for
use off license as an adjunct to compression bandaging for the treatment of chronic
venous leg ulcers by SIGN[7] as this has been shown to improve healing rates[8].

Adverse effects
Common side effects are belching, bloating, stomach discomfort or upset, nausea,
vomiting, indigestion, dizziness, and flushing. Uncommon and rare side effects
include angina, palpitations, hypersensitivity, itchiness, rash, hives, bleeding,
hallucinations, arrhythmias, and aseptic meningitis.[3][2][5][6]

Contraindications include intolerance to pentoxifylline or other xanthine

derivatives, recent retinal or cerebral haemorrhage, and risk factors for
haemorrhage.[3]

Mechanism
Like other methylated xanthine derivatives, pentoxifylline is a competitive
nonselective phosphodiesterase inhibitor[9] which raises intracellular cAMP,
activates PKA, inhibits TNF[10][11] and leukotriene [12] synthesis, and reduces
inflammation and innate immunity.[12] In addition, pentoxifylline improves red
blood cell deformability (known as a haemorrheologic effect), reduces blood
viscosity and decreases the potential for platelet aggregation and thrombus
formation.[13] Pentoxifylline is also an antagonist at adenosine 2 receptors.[14]

Effect on seizure
In a study, the effect of pentoxifylline as a phosphodiestrase inhibitor was study
on the pentylenetetrazol-induced seziure in the wild-type mice. Pentoxifylline in
that study reduced the anti-convulsive effect of H-89 and reduced the seizure
threshold.[15]

Research
There is some evidence that pentoxifyllinenon can lower the levels of some
biomarkers in non-alcoholic steatohepatitis but evidence is insufficient to
determine if the drug is safe and effective for this use.[16] Animal studies have
been conducted exploring the use of pentoxifylline for erectile dysfunction and
also human studies on Peyronie's disease.[17][18]

See also
Lisofylline, an active metabolite of pentoxifylline
Propentofylline
References
Drugs.com drugs.com international listings for Pentoxifylline. Page accessed Feb
1, 206
 "PRODUCT INFORMATION TRENTAL� 400" (PDF). TGA eBusiness Services. sanofi-aventis
australia pty limited. 25 March 2010. Retrieved 3 February 2014.
"Trental, Pentoxil (pentoxifylline) dosing, indications, interactions, adverse
effects, and more". Medscape Reference. WebMD. Retrieved 3 February 2014.
Salhiyyah K, Senanayake E, Abdel-Hadi M, Booth A, Michaels JA (2012).
"Pentoxifylline for intermittent claudication". The Cochrane Database of Systematic
Reviews. 1: CD005262. doi:10.1002/14651858.CD005262.pub2. PMID 22258961.
"PENTOXIFYLLINE tablet, extended release [Apotex Corp.]". DailyMed. Apotex Corp.
February 2013. Retrieved 3 February 2014.
"Trental 400 - Summary of Product Characteristics (SPC)". electronic Medicines
Compendium. Sanofi. 10 October 2013. Retrieved 3 February 2014.
SIGN (2010) Management of chronic venous leg ulcers. Clinical guideline No. 120.
Scottish Intercollegiate Guidelines Network. www.sign.ac.uk ISBN 978-1-905813-66-7
Jull, Andrew B; Arroll, Bruce; Parag, Varsha; Waters, Jill (2012). "Pentoxifylline
for treating venous leg ulcers". Cochrane Database of Systematic Reviews.
doi:10.1002/14651858.CD001733.pub3. ISSN 1465-1858.
Essayan DM (2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy
and Clinical Immunology. 108 (5): 671�80. doi:10.1067/mai.2001.119555. PMID
11692087.
Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R (2008). "Insights into the
regulation of TNF-alpha production in human mononuclear cells: the effects of non-
specific phosphodiesterase inhibition". Clinics. 63 (3): 321�8. doi:10.1590/S1807-
59322008000300006. PMC 2664230?Freely accessible. PMID 18568240.
Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (1999). "Pentoxifylline
inhibits TNF-alpha production from human alveolar macrophages". American Journal of
Respiratory and Critical Care Medicine. 159 (2): 508�11.
doi:10.1164/ajrccm.159.2.9804085. PMID 9927365.
Peters-Golden M, Canetti C, Mancuso P, Coffey MJ (2005). "Leukotrienes:
underappreciated mediators of innate immune responses". Journal of Immunology. 174
(2): 589�94. doi:10.4049/jimmunol.174.2.589. PMID 15634873.
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.
Rodr�guez-Mor�n M, Guerrero-Romero F (2008). "Efficacy of pentoxifylline in the
management of microalbuminuria in patients with diabetes". Current Diabetes
Reviews. 4 (1): 55�62. doi:10.2174/157339908783502343. PMID 18220696.
Hosseini-Zare MS, Salehi F, Seyedi SY, Azami K, Ghadiri T, Mobasseri M, Gholizadeh
S, Beyer C, Sharifzadeh M (2011). "Effects of pentoxifylline and H-89 on
epileptogenic activity of bucladesine in pentylenetetrazol-treated mice". European
Journal of Pharmacology. 670 (2�3): 464�70. doi:10.1016/j.ejphar.2011.09.026. PMID
21946102.
Li W, Zheng L, Sheng C, Cheng X, Qing L, Qu S (2011). "Systematic review on the
treatment of pentoxifylline in patients with non-alcoholic fatty liver disease".
Lipids in Health and Disease. 10: 49. doi:10.1186/1476-511X-10-49. PMC 3088890?
Freely accessible. PMID 21477300.
El-Sakka, A. I. (2011). "Reversion of penile fibrosis: Current information and a
new horizon". Arab Journal of Urology. 9 (1): 49�55. doi:10.1016/j.aju.2011.03.013.
PMC 4149188?Freely accessible. PMID 26579268.
Anele, U. A.; Morrison, B. F.; Burnett, A. L. (2015). "Molecular pathophysiology
of priapism: Emerging targets". Current drug targets. 16 (5): 474�83. PMC 4430197?
Freely accessible. PMID 25392014.
External links