Pentoxifylline Treatment Group Research Articles

Effect of Add-on Pentoxifylline on Proteinuria in Membranous Glomerulonephritis: A 6-month Placebo-controlled Trial

Membranous glomerulonephritis (MGN) may cause proteinuria as the main complication and is a strong risk factor for end-stage renal disease. Current therapeutic regimens provide only partial renoprotection. Data derived from both animal and human studies provide a scientific basis for the use of pentoxifylline as an antiproteinuric agent. This study was designed to evaluate the antiproteinuric effect of add-on pentoxifylline therapy in non-diabetic patients with MGN. This was a double-blind, placebo-controlled trial. Non-diabetic patients with histologically proven MGN and urinary protein excretion (UPE) > 500 mg/24 h, entered a 6-month study period. Enrolled patients were selected from a university and three private clinics. Patients were assigned to one of the two treatment groups: pentoxifylline 400 mg two or three times a day, or matching placebo. Baseline and follow-up assessments included estimated glomerular filtration rate (eGFR) and UPE. Differences in the changes in variables within the placebo and pentoxifylline treatment groups during the study period were assessed using Friedman's test. Treatment with pentoxifylline for 6 months resulted in a significant reduction of mean UPE (p < 0.001) along with a slight, non-significant increase of eGFR, in comparison to the mean UPE and eGFR increase in the placebo group. This study showed that add-on therapy of pentoxifylline in MGN was beneficial, and could be considered as a potential new therapeutic indication for the drug in such kidney diseases.

Pentoxifylline treatment for protecting diabetic retinopaty in children with type 1 diabetes

The purpose of this study was to determine whether oral pentoxifylline (PTX) would improve retinal microvascular hemodynamics in children with type 1 diabetes mellitus (DM). Non-invasive ultrasonographic measurements were made in 56 type 1 diabetic patients. The diabetic patients were matched first in terms of age, diabetes duration, then one individual within each pair was randomized into a pentoxifylline group and a control group. Pentoxifylline was administered for 6 months. We investigated the change of peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistivity index (RI) of central retinal artery (CRA) at 6 months after pentoxifylline. We investigated the relationship between PI, RI and carotide cross-sectional compliance (C-CSC). In comparison to changes in CRA measurements between the two groups, the pentoxifylline treatment group had significantly lower PI values (p=0.01). The RI, PSV and EDV were lower in pentoxifylline group but not statistically different. There was a positive correlation between CRA PSV and carotid Vmax (cm/s) (r=0.29, p=0.02) and also C-CSC (r=0.27, p=0.03). In addition, there was a positive correlation between PI and C-CSC (r=0.3, p=0.02). In the pentoxifylline group there was a significant reduction in systolic blood pressure, diastolic blood pressure, microalbuminuria and an increase in HDL level. Our results suggest that pentoxifylline may have a protective action for diabetic retinopathy and might modulate risk factors for atherosclerosis in type 1 diabetes.

Pentoxifylline improves liver regeneration through down-regulation of TNF-α synthesis and TGF-β1 gene expression

To investigate the mechanism of pentoxifylline (PTX) improvement in liver regeneration. Rats were randomized into 4 groups: Control rats; Sham - sham-operation rats; Saline - 70% hepatectomy plus saline solution; PTX - 70% hepatectomy plus PTX. At 2 and 6 h after hepatectomy, aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) serum and hepatic tissue levels were determined. Tumor growth factor (TGF)-β1 gene expression in liver tissue was evaluated 24 h after hepatectomy by quantitative reverse transcriptase polymerase chain reaction analysis. Proliferation was analyzed by mitotic index and proliferating cell nuclear antigen (PCNA) staining 48 h after hepatectomy. TNF-α and IL-6 serum levels increased at 2 and 6 h after hepatectomy. At 2 h after hepatectomy serum PTX was reduced but not hepatic levels of TNF-α and IL-6. A decrease in liver TGF-β1 gene expression and an increase in mitotic index and PCNA after hepatectomy were observed in the PTX treatment group in comparison to the saline group. PTX improves liver regeneration by a mechanism related to down regulation of TNF-α production and TGF-β1 gene expression.

Effectiveness of pentoxifylline on the cross-sectional area of intima media thickness and functions of the common carotid artery in adolescents with type 1 diabetes

The aim of the present study was to evaluate the effect of oral pentoxifylline on the cross-sectional area of intima media thickness (CSA-IMT) and functions of the common carotid artery, a marker of early atherosclerosis, in adolescents with type 1 diabetes. Non-invasive ultrasonographic measurements were made in 56 type 1 diabetic patients. The diabetic patients were matched first in terms of age, diabetes duration, major cardiovascular risk factors, including anthropometric and metabolic parameters as well as ultrasonographic measurements, then one individual within each pair randomized into a pentoxifylline group and a placebo (control) group (i.e., 32 on pentoxifylline group and 24 on placebo). Pentoxifylline was administered for 6 months. We investigated the change of CSA-IMT, compliance, distensibility, diastolic wall stress (DWS), and incremental elastic modulus of the common carotid artery at 6 months after pentoxifylline. In comparison of changes in common carotid artery measurements between the two groups, the pentoxifylline treatment group had significantly higher values than the controls for CSA-IMT (-2.6 +/- 0.1 vs. 0.7 +/- 0.4 mm2, p = 0.001) and for DWS (-0.38 +/- 0.02 vs. -0.05 +/- 0.05 mm Hg x 10(2), p < 0.001). In a multivariate regression model for all patients, being in pentoxifylline group was the best predictor of the change DWS (beta = -0.52, p < 0.001). Our preliminary results suggest that pentoxifylline has an antiatherogenic action and might modulate risk factors for atherosclerosis in type 1 diabetes.

The Effects of the Pentoxifylline on Survival of the Skin Flaps in Streptozotocin-Diabetic Rats

Skin flaps are frequently performed for diabetic patients in spite of countless detrimental effects of diabetes on flap survival. This study was planned because only a few clinical experiments have been performed on the effect of pentoxifylline (PTX) on the flaps in diabetic-animals. We studied 4 groups of rats: group 1, diabetic PTX treatment; group 2, diabetic control; group 3, nondiabetic PTX treatment; group 4, nondiabetic control. For the diabetic groups, diabetes mellitus was induced via intraperitoneal injection of streptozotocin (55 mg/kg). For treatment groups, PTX injections were started at the end of the 6th week of the experiment and procedures were carried out for 4 weeks during the experiment. Modified McFarlane flaps were elevated from all animals at the end of the 10th week of the experiment. Surviving areas of the flaps were measured at the end of the 11th week. Flap survival of the nondiabetic control and diabetic PTX treatment groups were significantly higher than of the diabetic control group (P < 0.01). Also, flap survival of the diabetic PTX treatment group was not statistically different than of the nondiabetic control group, but flap survival of the nondiabetic PTX treatment group was not statistically different from that of the nondiabetic control group. PTX appears to help decrease the harmful effects of diabetes on survival of the skin flaps.

Enhancement of recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced new bone formation by concurrent treatment with parathyroid hormone and a phosphodiesterase inhibitor, pentoxifylline.

We investigated the enhancement of new bone |formation elicited ectopically by recombinant human bone morphogenetic protein-2 (rhBMP-2), using parathyroid hormone (PTH) and a phosphodiesterase inhibitor (PDEi), pentoxifylline (PTX), in an animal model. Collagen sponge sheet discs containing rhBMP were implanted onto the back muscles of mice. PTX alone (200 mg/kg body weight [BW]), PTH(1-34) (10 microg/kg BW), PTX plus PTH (200 mg/kg BW and 10 microg/kg BW, respectively), or vehicle (control) were injected subcutaneously daily for 3 weeks after implantation. At the end of this period, rhBMP-2-induced ectopic ossicles were harvested from each group of animals. Ossicles from the PTX-treated group were significantly larger in size, with unchanged bone mineral density (BMD), as compared with the ossicles from the controls. In contrast, the ossicles from the PTH-treated group had significantly higher BMD, but showed no difference in size when compared with those from the control animals. The ossicles of the PTX + PTH treatment group were significantly larger than those of the control and PTH treatment groups. In addition, the BMD of the harvested tissues from the PTX + PTH treatment group was signifi-cantly higher than that of tissues from the control and PTX treatment groups. Although the calcium content of ossicles was significantly higher in the PTX-, PTH-, and PTX + PTH-treated groups than in the control group, the Ca content of ossicles from the PTH + PTX-treated group was highest (two times that of controls), followed by the PTH- and PTX-treated groups.

Pharmacokinetic and Tolerability Assessment of a Pediatric Oral Formulation of Pentoxifylline in Kawasaki Disease

Background: In infants and children, treatment of Kawasaki disease (KD) with high-dose intravenous immunoglobulin (IVIG) and acetylsalicylic acid ([ASA] aspirin) diminishes inflammatory response and reduces the risk for coronary artery abnormalities. However, patients with high serum concentrations of tumor necrosis factor (TNF)-alpha, which is associated with vascular damage, may develop coronary artery lesions even with treatment. The hemorheologic agent pentoxifylline blocks the production of TNF-alpha and may be an appropriate adjunctive therapy to IVIG and ASA. Objective: The objective of this study was to assess the pharmacokinetic characteristics and tolerability of a new oral syrup formulation of pentoxifylline as an adjunct to IVIG and ASA in the treatment of KD in children. Methods: Hospitalized boys and girls aged 6 months to 5 years and who were diagnosed with KD within the first 10 days of illness were eligible. Patients were assigned to 1 of 4 pentoxifylline treatment groups, by dose level (dose levels 1, 2, 3, and 4: 10, 15, 20, and 25 mg/kg daily, respectively, divided into 3 doses). Six plasma samples collected at the time the first dose was administered, and 4 samples collected after administration of the last dose on study day 6, were assessed by high-performance liquid chromatography using noncompartmental and 1-compartment pharmacokinetic analyses for pentoxifylline and its active metabolite (M-1). TNF-alpha levels on days 1 and 6 were assessed using electroimmunoassay. Results: Fourteen boys and 10 girls were enrolled. The mean age, body weight, and illness day at study entry were 34.5 months, 13.8 kg, and 6, respectively. Pentoxifylline exhibited nonlinear kinetic characteristics, with median area under the plasma concentration–time curve from time 0 to infinity(AUC 0–∞) values of 622, 3428, 8416, and 10,347 ng/mL · h for dose levels 1 to 4, respectively, on study day 1. Pentoxifylline noncompartmental oral clearance and volume of distribution were significantly lower, and dose-normalized AUC 0–∞ was significantly higher, for dose level 3 than dose level 1. M-1 parameters were not significantly different between dose levels. No accumulation of pentoxifylline or M-1 was noted. Fifteen of 24 patients (63%) reported mild to moderate adverse events that may or may not have been treatment related. Frequency and severity did not differ significantly between dose levels. Conclusions: In the children in this study, pentoxifylline was well tolerated at the doses studied. No notable differences in clinical outcomes were observed between dose levels, and dose levels 3 and 4 (20 and 25 mg/kg daily, respectively) resulted in similar exposure to both pentoxifylline and M-1. Future efficacy and tolerability studies should use a daily dose of 20 mg/kg of pentoxifylline in acute KD.

Procedure costs and outcomes associated with pharmacologic management of peripheral arterial disease in the department of defense

This study was undertaken to determine if differences existed between pharmacologic treatments of peripheral arterial disease (PAD) with respect to PAD-related costs and health care outcomes in the United States Department of Defense health care system. We performed a retrospective review of hospital and prescription data to explore the effects of at least 90 days of aspirin, pentoxifylline, papaverine, or dipyridamole on 4 PAD-related outcomes: number of PAD-related invasive procedures (INV), number of PAD-related examination procedures (EXM), number of PAD-related hospitalization days (HDAYS), and cost of PAD-related procedures (COST) during 5 years. A covariate representing the number of PAD-related hospitalizations before the study period was used to attempt to control for severity of disease state. General linear models were used in the analyses. A statistically significant difference was seen between treatment groups for a linear combination of INV, EXM, HDAYS, and COST when controlling for past PAD-related hospitalizations ( P < 0.014). A statistically significant relationship existed between treatment groups and INV ( P < 0.041). The pentoxifylline treatment group had a statistically significant higher covariate-adjusted mean INV compared with the aspirin treatment group ( P < 0.043). Also, PAD-related past hospitalizations were significantly related to EXM ( P < 0.006). Our results appear to support the use of aspirin as a preventive treatment in PAD compared with pentoxifylline or dipyridamole.

PCV15 Study of Procedure Costs And Outcomes Associated with the Pharmacological Treatment of Arterial Disease And Intermittant Claudication in the Department of Claudication in the Department of Defense

OBJECTIVE: The purpose of this study was to determine if differences existed between pharmacological treatments of peripheral arterial disease (and intermittent claudication) (PAD/IC) with respect to PAD/IC-related costs and health care outcomes in the Department of Defense (DOD) health care system. METHODS: A retrospective review of hospital and prescription data was performed to explore the effects of an exposure to at least 90 days of either aspirin, pentoxifylline, or dypiridamole on various PAD-related outcomes. The outcomes under study were the number of PAD-related invasive procedures performed (INV), number of PAD-related examination procedures performed (EXM), number of PAD-related hospitalization days incurred (HDAYS), and the cost of PAD-related procedures performed (COST). The study period encompassed five years. A covariate representing the pre-study period number of PAD-related hospitalizations was used to attempt to control for severity of disease state. General linear models (GLM) were used in the analyses. RESULTS: A GLM showed a statistically significant difference among the treatment groups for a linear combination of INV, EXM, HDAYS, and COST when controlling for past PAD-related hospitalizations (p < 0.02). A statistically significant relationship was also found to exist between treatment groups and INV (p < 0.04). The pentoxifylline treatment group was shown to have a statistically significant higher covariate-adjusted mean INV when compared to the aspirin treatment group by a post-hoc T test adjusted for alpha inflation (p = 0.04). Also, PAD-related past hospitalizations showed a statistically significant relationship with a EXM (p < 0.006). CONCLUSION: The results appear to support the use of aspirin in PAD as a preventative treatment.