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Journal of the American Academy of... Apr 1994Pentoxifylline (oxpentifylline) is a methylxanthine derivative with potent hemorrheologic properties. In the United States it is marketed for the treatment of... (Review)
Review
Pentoxifylline (oxpentifylline) is a methylxanthine derivative with potent hemorrheologic properties. In the United States it is marketed for the treatment of intermittent claudication. Human and animal studies have shown that pentoxifylline therapy results in a variety of physiological changes at the cellular level, which may be important in treating a diverse group of human afflictions. Immune modulation includes increased leukocyte deformability and chemotaxis, decreased endothelial leukocyte adhesion, decreased neutrophil degranulation and release of superoxides, decreased production of monocyte-derived tumor necrosis factor, decreased leukocyte responsiveness to interleukin 1 and tumor necrosis factor, inhibition of T and B lymphocyte activation, and decreased natural killer cell activity. Hypercoagulable states improve through decreased platelet aggregation and adhesion, increased plasminogen activator, increased plasmin, increased antithrombin III, decreased fibrinogen, decreased alpha 2-antiplasmin, decreased alpha 1-antitrypsin, and decreased alpha 2-macroglobulin. Wound healing and connective tissue disorders may respond to an increase in fibroblast collagenases and decreased collagen, fibronectin, and glycosaminoglycan production. Fibroblast responsiveness to tumor necrosis factor is also diminished. Potential medical uses of pentoxifylline are reviewed.
Topics: Animals; Blood Coagulation; Connective Tissue; Dose-Response Relationship, Drug; Drug Interactions; Fibrinolysis; Humans; Pentoxifylline; Skin Diseases; Skin Neoplasms; Viscosity; Wound Healing
PubMed: 8157787
DOI: 10.1016/s0190-9622(94)70069-9 -
Inflammation & Allergy Drug Targets Dec 2012Pentoxifylline is methylxanthine derivative which is used in microcirculatory disorders as a vasoactive drug. Novel immunomodulatory properties of pentoxifylline have... (Review)
Review
Pentoxifylline is methylxanthine derivative which is used in microcirculatory disorders as a vasoactive drug. Novel immunomodulatory properties of pentoxifylline have been reported including the down regulation of tumour necrosis factor-α synthesis and other inflammatory cytokines. Studies have shown that pentoxifylline might be efficacious in a wide spectrum of skin diseases. This article focuses on the use of pentoxifylline which is a safe and cheap drug in various dermatological disorders.
Topics: Animals; Cytokines; Down-Regulation; Drug Costs; Humans; Microcirculation; Pentoxifylline; Phosphodiesterase Inhibitors; Skin Diseases; Tumor Necrosis Factor-alpha
PubMed: 22680624
DOI: 10.2174/187152812803590028 -
The British Journal of Oral &... Apr 2017Pentoxifylline has been used to treat complications related to fibrosis for over 20 years. Formerly used to treat those after radiotherapy such as osteoradionecrosis... (Review)
Review
Pentoxifylline has been used to treat complications related to fibrosis for over 20 years. Formerly used to treat those after radiotherapy such as osteoradionecrosis (ORN), it is now being tried for medication-related osteonecrosis of the jaw (MRONJ), which can occur after prolonged use of bisphosphonates. We review theories on the formation of fibrosis in patients with ORN, discuss the pharmacology of pentoxifylline and vitamin E, and report published outcomes. To our knowledge no prospective randomised controlled trial has investigated the benefits of these agents in cases of ORN, but reported outcomes in many published case series are encouraging.
Topics: Humans; Jaw Diseases; Osteoradionecrosis; Pentoxifylline
PubMed: 28034471
DOI: 10.1016/j.bjoms.2016.12.006 -
The Cochrane Database of Systematic... Oct 2009Alcoholic hepatitis is a life-threatening disease, with an average mortality of approximately 40%. There is no widely accepted, effective treatment for alcoholic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alcoholic hepatitis is a life-threatening disease, with an average mortality of approximately 40%. There is no widely accepted, effective treatment for alcoholic hepatitis. Pentoxifylline is used to treat alcoholic hepatitis, but there has been no systematic review to assess its effects.
OBJECTIVES
To assess the benefits and harms of pentoxifylline in alcoholic hepatitis.
SEARCH STRATEGY
The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, clinicaltrials.gov, and full text searches were conducted until August 2009. Manufacturers and authors were contacted.
SELECTION CRITERIA
All randomised clinical trials of pentoxifylline in participants with alcoholic hepatitis compared to control were selected for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors extracted data and evaluated the risk of bias. RevMan Analysis was used for statistical analysis of dichotomous data with risk ratio (RR) and of continuous data with mean difference (MD), both with 95% confidence intervals (CI). Trial sequential analysis (TSA) was also used for statistical analysis of dichotomous and continuous data in order to control for random error. Where data were only available from one trial, we used Fisher's exact test or Student's t-test.
MAIN RESULTS
Five trials, with a total of 336 randomised participants, were included. A total of 105 participants (31%) died. Of the five included trials, four (80%) had a high risk of bias. Meta-analysis using all five trials showed that pentoxifylline reduced mortality compared with control (RR 0.64; 95% CI 0.46 to 0.89). However, this result was not supported by trial sequential analysis, which adjusts for multiple testing on accumulating data. Furthermore, four of the five trials were judged to have a high risk of bias, thus risking an overestimated intervention effect. Meta-analysis showed that pentoxifylline reduced the hepatic-related mortality due to hepatorenal syndrome (RR 0.40; 95% CI 0.22 to 0.71), but trial sequential analysis did not support this result. Data from one trial suggests that pentoxifylline may increase the occurrence of serious and non-serious adverse events compared to control.
AUTHORS' CONCLUSIONS
The current available data may indicate a possible positive intervention effect of pentoxifylline on all-cause mortality and mortality due to hepatorenal syndrome, and conversely, an increase in serious and non-serious adverse events. However, the evidence is not firm; no conclusions can be drawn regarding whether pentoxifylline has a positive, negative, or neutral effect on participants with alcoholic hepatitis.
Topics: Cause of Death; Hepatitis, Alcoholic; Humans; Pentoxifylline; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha
PubMed: 19821406
DOI: 10.1002/14651858.CD007339.pub2 -
Journal of the American Animal Hospital... 2001
Review
Topics: Animals; Dog Diseases; Dogs; Hematologic Agents; Pentoxifylline; Veterinary Drugs
PubMed: 11361111
DOI: 10.5326/15473317-37-3-218 -
The Cochrane Database of Systematic... Dec 2012Healing of venous leg ulcers is improved by the use of compression bandaging but some venous ulcers remain unhealed, and some people are unsuitable for compression... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Healing of venous leg ulcers is improved by the use of compression bandaging but some venous ulcers remain unhealed, and some people are unsuitable for compression therapy. Pentoxifylline, a drug which helps blood flow, has been used to treat venous leg ulcers.
OBJECTIVES
To assess the effects of pentoxifylline (oxpentifylline or Trental 400) for treating venous leg ulcers, compared with a placebo or other therapies, in the presence or absence of compression therapy.
SEARCH METHODS
For this fifth update we searched the Cochrane Wounds Group Specialised Register (searched 20 July 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7); Ovid MEDLINE (2010 to July Week 2 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, July 19, 2012); Ovid EMBASE (2010 to 2012 Week 28); and EBSCO CINAHL (2010 to July 13 2012).
SELECTION CRITERIA
Randomised trials comparing pentoxifylline with placebo or other therapy in the presence or absence of compression, in people with venous leg ulcers.
DATA COLLECTION AND ANALYSIS
One review author extracted and summarised details from eligible trials using a coding sheet. One other review author independently verified data extraction.
MAIN RESULTS
No new trials were identified for this update. We included twelve trials involving 864 participants. The quality of trials was variable. Eleven trials compared pentoxifylline with placebo or no treatment. Pentoxifylline is more effective than placebo in terms of complete ulcer healing or significant improvement (RR 1.70, 95% CI 1.30 to 2.24). Pentoxifylline plus compression is more effective than placebo plus compression (RR 1.56, 95% CI 1.14 to 2.13). Pentoxifylline in the absence of compression appears to be more effective than placebo or no treatment (RR 2.25, 95% CI 1.49 to 3.39).More adverse effects were reported in people receiving pentoxifylline (RR 1.56, 95% CI 1.10 to 2.22). Nearly three-quarters (72%) of the reported adverse effects were gastrointestinal.
AUTHORS' CONCLUSIONS
Pentoxifylline is an effective adjunct to compression bandaging for treating venous ulcers and may be effective in the absence of compression. The majority of adverse effects were gastrointestinal disturbances.
Topics: Administration, Oral; Bandages; Combined Modality Therapy; Fibrinolytic Agents; Humans; Leg Ulcer; Pentoxifylline; Polydeoxyribonucleotides; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 23235582
DOI: 10.1002/14651858.CD001733.pub3 -
Paediatric Drugs Oct 2010Sepsis, necrotizing enterocolitis (NEC), and chronic lung disease (CLD) in preterm neonates are associated with significant mortality and morbidity, including long-term... (Review)
Review
Sepsis, necrotizing enterocolitis (NEC), and chronic lung disease (CLD) in preterm neonates are associated with significant mortality and morbidity, including long-term neurodevelopmental impairment and socioeconomic burden. Safe and effective drugs for the prevention and treatment of these conditions are urgently needed. Pentoxifylline, a synthetic theobromine derivative, is a non-steroidal immunomodulating agent with unique hemorrheologic effects which has been used in a range of infectious, vascular, and inflammatory conditions in adults and children. The unique properties of pentoxifylline explain its potential benefits in preterm neonates with sepsis, NEC, and CLD, conditions characterized by activation of the inflammatory cytokine cascade, free radical toxicity, and impaired microcirculation. Pentoxifylline has anti-inflammatory properties resulting from inhibition of erythrocyte phosphodiesterase. It lowers blood viscosity and improves microcirculation and tissue perfusion. As a phosphodiesterase inhibitor, pentoxifylline downregulates pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Methylxanthines, including caffeine, theophylline, and theobromine are relatively non-toxic drugs; of these, theobromine is the least toxic. Pentoxifylline-related significant adverse events are thus very rare. Unlike other methylxanthines, pentoxifylline does not have significant cardiac and bronchodilating effects at therapeutic doses. Although it is contraindicated in adults with recent cerebral hemorrhage due to its effect on platelets, red blood cells, and plasma fibrinogen levels, no significant adverse effects including thrombocytopenia and bleeding have been reported in critically ill preterm neonates with sepsis or NEC after treatment with pentoxifylline. Based on data from pilot randomized trials and observational studies, our systematic review suggests that pentoxifylline may reduce mortality and/or morbidity in preterm neonates with sepsis, NEC, and CLD. Results of experimental studies also indicate that pentoxifylline may potentially be beneficial in meconium aspiration syndrome and hypoxic ischemic encephalopathy. Given the substantial burden of sepsis, NEC, and CLD in high-risk preterm neonates, and the findings of this systematic review, pentoxifylline needs to be evaluated urgently as a preventative and therapeutic agent for these conditions in randomized controlled trials that can detect minimal clinically significant effect sizes. Further clinical and experimental studies are also necessary to evaluate whether pentoxifylline is safe and effective in meconium aspiration syndrome and hypoxic ischemic encephalopathy.
Topics: Animals; Humans; Infant, Newborn; Lung Diseases; Meconium Aspiration Syndrome; Pentoxifylline; Persistent Fetal Circulation Syndrome; Premature Birth; Sepsis
PubMed: 20799759
DOI: 10.2165/11532600-000000000-00000 -
Inflammopharmacology Jun 2022The existing pandemic viral infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) leads to coronavirus disease 2019 (Covid-19).... (Review)
Review
The existing pandemic viral infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) leads to coronavirus disease 2019 (Covid-19). SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as an entry-point into affected cells and down-regulation of ACE2 by this virus triggers the release of pro-inflammatory cytokines and up-regulation of angiotensin II. These changes may lead to hypercytokinemia and the development of cytokine storm with the development of acute lung injury and acute respiratory distress syndrome. Different repurposed had been in use in the management of Covid-19, one of these agents is pentoxifylline (PTX) which has anti-inflammatory and antioxidant properties. Therefore, the objective of the present mini-review is to highlight the potential role of PTX in Covid-19 regarding its anti-inflammatory and antioxidant effects. PTX is a non-selective phosphodiesterase inhibitor that increases intracellular cyclic adenosine monophosphate which stimulates protein kinase A and inhibits leukotriene and tumor necrosis factor. PTX has antiviral, anti-inflammatory and immunomodulatory effects, thus it may attenuate SARS-CoV-2-induced hyperinflammation and related complications. As well, PTX can reduce hyper-viscosity and coagulopathy in Covid-19 through increasing red blood cell deformability and inhibition of platelet aggregations. In conclusion, PTX is a non-selective phosphodiesterase drug, that has anti-inflammatory and antioxidant effects thereby can reduce SARS-CoV-2 infection-hyperinflammation and oxidative stress. Besides, PTX improves red blood cells (RBCs) deformability and reduces blood viscosity so can mitigate Covid-19-induced hyper-viscosity and RBCs hyper-aggregation which is linked with the development of coagulopathy. Taken together, PTX seems to be an effective agent against Covid-19 severity.
Topics: Angiotensin-Converting Enzyme 2; Anti-Inflammatory Agents; Antioxidants; Cytokine Release Syndrome; Humans; Pentoxifylline; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35486310
DOI: 10.1007/s10787-022-00993-1 -
Current Pharmaceutical Biotechnology 2018Pentoxifylline (PTX) is a drug commonly used in the treatment of intermittent claudication. However, numerous research groups report that PTX also may potentially be... (Review)
Review
BACKGROUND
Pentoxifylline (PTX) is a drug commonly used in the treatment of intermittent claudication. However, numerous research groups report that PTX also may potentially be used in the anticancer therapy following one of the main trends in the nowadays medicine - combined anticancer therapy.
SCOPE OF REVIEW
The review concentrates on the reports revealing the potential use of PTX in cancer treatment. Major Conclusion: PTX is described to possess several properties which may be exploited in cancer treatment. The drug reportedly not only has anticancer activity itself, but also increases cancer cells susceptibility to radiation therapy and, additionally, reduces long-term side effects of this therapy. Furthermore, numerous research groups report that PTX may increase the anticancer potential of commonly used anticancer drugs such as cisplatin or doxorubicin as well as reduce side effects of these drugs.
SIGNIFICANCE
PTX should be considered as a potential drug in the combined anticancer therapy.
Topics: Animals; Antineoplastic Agents; Humans; Neoplasms; Pentoxifylline
PubMed: 29804530
DOI: 10.2174/1389201019666180528084641 -
The Cochrane Database of Systematic... Apr 2008There is increasing evidence that capillary occlusion plays an important part in the development of diabetic retinopathy. Disaggregants, such as pentoxyfilline may... (Review)
Review
BACKGROUND
There is increasing evidence that capillary occlusion plays an important part in the development of diabetic retinopathy. Disaggregants, such as pentoxyfilline may influence the outcome and progression of diabetic retinopathy, but no systematic review of the literature on its efficacy and safety has been published to examine this hypothesis.
OBJECTIVES
The aim of the current research was to review the literature in a systematic way in order to assess the effects of pentoxyfilline for diabetic retinopathy in methodologically robust trials. The null hypothesis was that pentoxyfilline has no influence on the progression of diabetic retinopathy or blindness.
SEARCH STRATEGY
A systematic search of electronic databases was carried out to identify publications. Relevant papers, written in any language, were accessed and assessed for data.
SELECTION CRITERIA
Only randomized controlled clinical trials (RCTs) evaluating the effects of pentoxyfilline in the treatment of diabetic retinopathy were to be included.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion criteria and for risk of bias.
MAIN RESULTS
A total of 97 publications were identified by the electronic search and two authors checked the abstracts. Of these, 17 were identified as potentially relevant trials providing information about treatment of patients with diabetic retinopathy using pentoxyfilline and were read in full. Unfortunately, no publication fulfilled our inclusion criteria.
AUTHORS' CONCLUSIONS
No sound research to date has examined the treatment of diabetic retinopathy with pentoxyfilline in such a way as to indicate whether this form of intervention has a significant impact on the natural history of this clinical condition. The potential role of this substance in the treatment of diabetic retinopathy remains open to debate, and it is suggested that future research focusing on patient-relevant outcomes takes the opportunity of addressing this important issue directly.
Topics: Diabetic Retinopathy; Humans; Pentoxifylline; Vasodilator Agents
PubMed: 18425965
DOI: 10.1002/14651858.CD006693.pub2