Oral Administration Of Pentoxifylline Research Articles

Oral Administration of Pentoxifylline Reduces Endometriosis-Like Lesions in a Nude Mouse Model.

Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm3 vs 276.75 ± 94.30 mm3 and 145.33 ± 38.20 mm3, respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm2) versus group 2 (1.35 ± 0.43 mm2) and control (2.84 ± 0.60 mm2; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

Pharmacokinetics of pentoxifylline in dogs after oral and intravenous administration.

To evaluate the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl-metabolite, metabolite 1 (M1), in dogs after IV administration of a single dose and oral administration of multiple doses. 7 sexually intact, female, mixed-breed dogs. A crossover study design was used so that each of the dogs received all treatments in random order. A drug-free period of 5 days was allowed between treatments. Treatments included IV administration of a single dose of PTX (15 mg/kg of body weight), oral administration of PTX with food at a dosage of 15 mg/kg (q 8 h) for 5 days, and oral administration of PTX without food at a dosage of 15 mg/kg (q 8 h) for 5 days. Blood samples were taken at 0.25, 0.5, 1, 1.5, 2, 2.5, and 3 hours after the first and last dose of PTX was administered PO, and at 5, 10, 20, 40, 80, and 160 minutes after PTX was administered IV. PTX was rapidly absorbed and eliminated after oral administration. Mean bioavailability after oral administration ranged from 15 to 32% among treatment groups and was not affected by the presence of food. Higher plasma PTX concentrations and apparent bioavailability were observed after oral administration of the first dose, compared with the last dose during the 5-day treatment regimens. In dogs, oral administration of 15 mg of PTX/kg results in plasma concentrations similar to those produced by therapeutic doses in humans, and a three-times-a-day dosing regimen is the most appropriate.

Successful application of pentoxifylline in the treatment of HTLV-I associated myelopathy

Fifteen patients with human T-cell lymphotropic virus type-I (HTLV-I)-associated myelopathy (HAM) were treated in an uncontrolled preliminary trial by oral administration of pentoxifylline (PTX). Motor function, neurological evaluation, immunological markers and parameters were evaluated after four weeks. In 13 of the 15 patients, motor disability, especially spasticity, improved substantially. PTX suppressed spontaneous proliferation of peripheral blood mononuclear cells in 14 of the 15 patients at four weeks. No adverse effect was observed. We concluded that PTX may be a safe and beneficial agent for the treatment of HAM.

Pentoxifylline in idiopathic male-factor infertility: a review of its therapeutic efficacy after oral administration

Since the use of pentoxifylline has received much recent attention for its role in the treatment of male-factor infertility by in-vitro fertilization, there is now an increasing interest in its oral use. Therefore, results reported in the literature on the treatment of idiopathic male-factor infertility by oral administration of pentoxifylline were summarized and reviewed. None of the reports presented a valid rationale for the systematic use of pentoxifylline and the reported results were found to be conflicting. Because of poor study design or low statistical power, the published data did not support a beneficial role of the systemic use of pentoxifylline in idiopathic male-factor infertility. Prospective, double blind trials dealing with fecundity as the major outcome measure may provide the information needed.

Effect of Pentoxifylline on Treatment of Lower Limb Ulcers in Patients with Thalassemia Major

The possible healing effect of deferoxamine and pentoxifylline on persisting lower limb ulcers was studied in 51 patients with thalassemia major. The results indicated that the regular use of deferoxamine at an intravenous dose of 20 mg/kg did not affect the healing progress and the recurrence rate of these ulcers significantly On the contrary, the oral administration of pentoxifylline at a dose of 1,200 mg daily during the ulcer's healing time and at a low long-term maintenance dose of 400 mg daily during the ulcer-free intervals improved their healing ability impressively and diminished their recurrence rate significantly

Effect of Pentoxifylline on Treatment of Lower Limb Ulcers in Patients with Thalassemia Major

The possible healing effect of deferoxamine and pentoxifylline on persisting lower limb ulcers was studied in 51 patients with thalassemia major. The results indicated that the regular use of deferoxamine at an intravenous dose of 20 mg/kg did not affect the healing progress and the recurrence rate of these ulcers significantly. On the contrary, the oral administration of pentoxifylline at a dose of 1,200 mg daily during the ulcer's healing time and at a low long-term maintenance dose of 400 mg daily during the ulcer-free intervals improved their healing ability impressively and diminished their recurrence rate significantly.

Prevention of Regimen-Related Toxicities After Bone Marrow Transplantation by Pentoxifylline: A Prospective, Randomized Trial

Elevated levels of tumor necrosis factor alpha (TNF-alpha) have been reported to correlate with the development of transplant-related complications after bone marrow transplantation (BMT). In a recent phase I-II trial, oral administration of pentoxifylline (PTX), a xanthine derivative capable of downregulating TNF-alpha production in vitro, was reported to reduce morbidity and mortality in patients undergoing BMT. We conducted a prospective randomized trial of PTX therapy among 140 patients undergoing either allogeneic (n = 51) or autologous BMT (n = 89). Patients were randomized to receive (n = 70) or not receive (n = 70) oral PTX, 1,600 mg/d in four divided doses from day -8 until day + 100 post-BMT. The incidence of mucositis requiring morphine sulfate (MSO4) was similar in both groups (42.9%), with the mean number of days with MSO4 being 7.8 (SD = 3.4) in the PTX group versus 8.2 (SD = 3.4) in the control group (NS). The incidence of renal insufficiency was not affected by PTX administration (15.7% in the PTX group v 21.4% in the control group [NS]) and the highest serum creatinine value during the first 100 days post-BMT was 119 mumol/L (SD = 82.4) in the PTX group versus 103.9 mumol/L (SD = 57) in the control group (NS). The incidence of grade > or = 2 graft-versus-host disease was similar in each group (11/25 [44%] in the PTX group v 12/26 [46%] in the control group). No significant difference was observed in hematologic toxicity, transfusion requirements, duration of fever, and hepatic toxicity between the treatment groups. In conclusion, our study failed to show a prophylactic effect of PTX in transplant-related toxicities after BMT. On the basis of these findings, we cannot recommend that PTX be part of early mortality and morbidity prevention programs after BMT.

Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: a prospective, randomized trial

Elevated levels of tumor necrosis factor alpha (TNF-alpha) have been reported to correlate with the development of transplant-related complications after bone marrow transplantation (BMT). In a recent phase I-II trial, oral administration of pentoxifylline (PTX), a xanthine derivative capable of downregulating TNF-alpha production in vitro, was reported to reduce morbidity and mortality in patients undergoing BMT. We conducted a prospective randomized trial of PTX therapy among 140 patients undergoing either allogeneic (n = 51) or autologous BMT (n = 89). Patients were randomized to receive (n = 70) or not receive (n = 70) oral PTX, 1,600 mg/d in four divided doses from day -8 until day + 100 post-BMT. The incidence of mucositis requiring morphine sulfate (MSO4) was similar in both groups (42.9%), with the mean number of days with MSO4 being 7.8 (SD = 3.4) in the PTX group versus 8.2 (SD = 3.4) in the control group (NS). The incidence of renal insufficiency was not affected by PTX administration (15.7% in the PTX group v 21.4% in the control group [NS]) and the highest serum creatinine value during the first 100 days post-BMT was 119 mumol/L (SD = 82.4) in the PTX group versus 103.9 mumol/L (SD = 57) in the control group (NS). The incidence of grade > or = 2 graft-versus-host disease was similar in each group (11/25 [44%] in the PTX group v 12/26 [46%] in the control group). No significant difference was observed in hematologic toxicity, transfusion requirements, duration of fever, and hepatic toxicity between the treatment groups. In conclusion, our study failed to show a prophylactic effect of PTX in transplant-related toxicities after BMT. On the basis of these findings, we cannot recommend that PTX be part of early mortality and morbidity prevention programs after BMT.

Phosphodiesterase inhibitor pentoxifylline, a selective suppressor of T helper type 1‐ but not type 2‐associated lymphokine production, prevents induction of experimental autoimmune encephalomyelitis in Lewis rats

The phosphodiesterase inhibitor pentoxifylline (POX), which is known to have pharmacological effects in animal models of multiorgan failure and endotoxin-mediated shock, was tested for its immunosuppressive potential on T lymphocyte activation in vitro and in vivo. POX was found to have a profound inhibitory effect on both mitogen- and antigen-induced proliferation of CD4+ T cells in vitro. This inhibitory activity of the drug could be reproduced by treating T lymphocytes with cAMP analogues during stimulation. Responses of repeatedly in vitro stimulated cells were much more strongly inhibited by the drug and by cAMP analogues than responses of fresh resting lymphocytes. Furthermore, POX could drastically down-regulate tumor necrosis factor regulate production and to a lesser extent interleukin (IL)-2 secretion in activated T cells, but an excess of exogenous IL-2 did not override the antiproliferative effect of the drug. In contrast, the same doses of POX had no inhibitory effect on spontaneous or induced IL-4 and IL-6 production by short-term cultured T lymphocytes, indicating a selective sparing of T helper type 2 (Th2)-associated lymphokine functions by the drug. To test a potential use of POX as an antiinflammatory agent in T cell-mediated autoimmune disease, the influence of POX on myelin basic protein (MBP)-induced experimental autoimmune encephalomyelitis (EAE) was assessed. The onset of EAE in Lewis rats could almost completely be abrogated by oral administration of POX during the induction phase of disease. Lack of clinical symptoms in POX-treated animals coincided with a marked suppression of MBP-specific T cell reactivity in vitro, without any evidence for a generalized impairment of T cell activity. Collectively, our data suggest the potential use of xanthine derivatives of the POX type as a supporting antiinflammatory therapeutic agent in Th1 CD4+ T cell-mediated autoimmune diseases in animal models and possibly in man.

Effect of oral pentoxifylline therapy on venous lower extremity ulcers due to deep venous incompetence.

The effect of oral pentoxifylline, administered 1,200 mg/day (400 mg slow-release tablets tid) through six weeks, was studied in 10 patients with established deep venous incompetence and persisting venous ulcers. The following parameters were used for verification of the therapeutic result: venous patency (VP) and valvular competence (VC) assessed by means of Doppler ultrasound; venous refilling time (VRT) assessed by photoplethysmography; skin blood flow (SBF) at rest and after tiptoeing exercise, as well as skin perfusion pressure (SPP), both assessed by means of 99mtechnetium clearance technique. Finally, photo documentation of the tissue lesion was obtained, using a two-dimensional (max and min diameter = Dmax, Dmin) metered scale photo. There was an overall good response to the treatment, the studied parameters showing the following changes: VP and VC remained unchanged; VRT improved in 8 patients, SBF increased in 10; SPP slightly improved in 5; and Dmax and Dmin in all 10 patients. Removal or substantial diminution of the ulcers was obtained in 8 patients. These findings indicate that oral administration of pentoxifylline over a period of six weeks supports the conservative treatment and improves considerably the condition of patients with persisting venous ulcers.

Influence of pentoxifylline on erythrocyte deformability in peripheral occlusive arterial disease.

Impaired red cell deformability has been found in patients suffering from chronic peripheral vascular disorders, the implication being that microcirculatory blood flow is hindered and tissue hypoxaemia is aggravated. Measurement of erythrocyte deformability by a standard filtration technique for whole blood was carried out in 40 young healthy persons, in 25 untreated patients with peripheral occlusive arterial disease and in 25 patients with matching vascular disease, before and after a 6-weeks' oral treatment with 400 mg pentoxifylline 4-times daily. The filtration rates were significantly lower in the patient groups compared to those of healthy volunteers. After the oral administration of pentoxifylline, a significant increase in filtration rates was observed pointing to an improvement in erythrocyte deformability. The findings suggest that by improving erythrocyte deformability pentoxifylline positively influences the microcirculatory blood fluidity, an important factor for efficient therapy in peripheral arterial occlusive disease.

The use of pentoxifylline in the treatment of ischaemic heart disease

SummaryForty patients suffering from ischaemic heart disease were treated orally with 600 mg pentoxifylline daily for periods ranging from 25 to 30 days to assess its therapeutic potential in the treatment of this disorder. The results showed that 35 (87.5%) patients were able to discontinue or reduce their consumption of nitroglycerin. Physical exercise tolerance was observed in 30 (75%), and 34 (85%) patients reported an improvement in their general condition. Pentoxifylline produced a positive effect on the ECG, deceleration of pulse rate and normalization of R and T waves being registered in 22 (55 %) patients. Analysis of the cardiac cycle showed a reduction in isometric contraction time, a prolongation of ejection time and diastole, and an increase in internal systolic pressure. Tachycardia disappeared or was diminished considerably in 20 (77%) of 26 patients in whom it had been detected previously. No side-effects were reported with the oral administration of pentoxifylline.