The bioavailability of a generic preparation of pentoxifylline sustained-release (SR) tablet was evaluated in comparison with a proprietary product (Trental 400). For the study, 12 healthy male volunteers participated; the study was conducted according to a randomized, two-way crossover design. The bioavailability was compared using the parameters total area under the plasma level-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was observed between the values of the two products in all three parameters. The 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity values of the generic pentoxifylline over those of Trental 400 was found to lie between 0.83 and 1.00, while that of the parameter Cmax was between 0.91 and 1.29. In addition, elimination half-life t1/2 and apparent volume of distribution Vd were calculated. There was no statistically significant difference between the t1/2 Vd values obtained from the data of the two preparations.
A simple high-performance liquid chromatographic method using ultraviolet detection was developed for the determination of pentoxifylline in human plasma. Prior to analysis, pentoxifylline and the internal standard (chloramphenicol) were extracted from plasma sample using dichloromethane. The mobile phase comprised 0.02 M phosphoric acid adjusted to pH 4, methanol and tetrahydrofuran (55:45:1, v/v). Analysis was run at a flow-rate of 1.4 ml/min with the detector operated at a wavelength of 273 nm. The method was specific and sensitive with a detection limit of approximately 3.0 ng/ml at a signal to noise ratio of 3:1, while the limit of quantification was 12.5 ng/ml. Mean recovery value of the extraction procedure was about 99.9%, while the within-day and between-day coefficient of variation and percent error values of the assay method were all less than 10.0%. The calibration curve was linear over a concentration range of 12.5-400.0 ng/ml.
The prevalence of nonalcoholic fatty liver disease (NAFLD) has significantly increased over the last decades. Despite existence of several interventions, there remains unclear which interventions work the best.
Matched MeSH terms: Pentoxifylline/therapeutic use
Fibrosis is a potentially debilitating disease with high morbidity rates. It is estimated that half of all deaths that occur in the USA are attributed to fibrotic disorders. Fibrotic disorders are characterized primarily by disruption in the extracellular matrix deposition and breakdown equilibrium, leading to the accumulation of excessive amounts of extracellular matrix. Given the potentially high prevalence of fibrosis and the paucity of agents currently available for the treatment of this disease, there is an urgent need for the identification of drugs that can be utilized to treat the disease. Pentoxifylline is a methylxanthine derivative that is currently approved for the treatment of vascular diseases, in particular, claudication. Pentoxifylline has three main properties: improving the rheological properties of blood, anti-inflammatory, and antioxidative. Recently, the effectiveness of pentoxifylline in the treatment of fibrosis via attenuating and reversing fibrotic lesions has been demonstrated in several clinical trials and animal studies. As a result of the limited availability of antifibrotic agents in the long-term treatment of fibrosis that can attenuate and even reverse fibrotic lesions effectively, it would be of particular importance to consider the potential clinical utility of pentoxifylline in the treatment of fibrosis. Thus, this paper discusses the evolving roles of pentoxifylline in the treatment of different types of fibrosis.
Several pharmacological agents have been found to alter systemic concentrations and/or the activity of different cytokines via a variety of mechanisms, including changes in biosynthesis, secretion, and/or stability. Pentoxifylline (PTX), which is a methylxanthine derivative for example, has multiple effects on the immune system, but inhibition of pro-inflammatory cytokine release predominates. In this study we aimed to evaluate the influence of PTX on plasma levels of tumor necrosis factor (TNF) alpha and interleukin (IL)-6 in newborn infants with sepsis. The study included 20 infants with neonatal sepsis. In all subjects blood samples for serum C-reactive protein, TNF alpha and IL-6 determinations were received before giving PTX and at the 12th and 24th hours following PTX. In addition, white blood cell was counted before giving PTX and on the 3rd and 7th day following PTX. The infants were randomly divided into two groups. Firstly, PTX was used in infants who were successively admitted to the clinic and the subsequent infants were accepted as a control group. Of 20 infants, 13 infants received PTX and seven infants did not. We did not find any difference in the leukocyte count, serum C-reactive protein level, TNF alpha and IL-6 levels between the two groups of patients (P>0.05). While three infants died in the group of receiving PTX, death was not recorded in the group of non-receiving PTX (P>0.05). Our findings showed that PTX treatment did not affect leukocyte counts, serum CRP levels, TNF alpha and IL-6 levels and death ratio in newborn infants with sepsis. The last result may be due to the fact that the number of patients in the study was very small. We think that more extensive and controlled studies should be performed about this subject.
PURPOSE: To discuss the current rationale for the use of specific and nonspecific therapies for thrombotic microangiopathy in thrombocytopenia-associated pediatric multiple organ failure syndromes. Methods: Pertinent PubMed and MEDLINE citations and proceedings of recent critical care meeting presentations were reviewed. RESULTS: Critical care clinicians have reported using antithrombin III concentrate, protein C concentrate, activated protein C, prostacyclin and its analogues, heparin, tissue factor pathway inhibitor concentrate, plasma infusion, plasma exchange, whole blood exchange, pentoxifylline, tissue plasminogen activator, urokinase, and streptokinase with perceived therapeutic benefits in patients with thrombocytopenia-associated multiple organ failure, including those with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, disseminated intravascular coagulation syndrome, and secondary thrombotic microangiopathy syndrome without prolonged prothrombin time/activated partial thromboplastin time. CONCLUSION: Assuming that underlying disease is remediable, a consensus has developed that thrombotic microangiopathy is a therapeutic target in children with thrombocytopenia-associated multiple organ failure syndromes. Studies are warranted to delineate efficacious use of specific and nonspecific therapies to prevent and reverse thrombotic microangiopathy in these patients.