Oral Administration Of Beraprost Sodium Research Articles

Effect of beraprost on pulmonary hypertension due to left ventricular systolic dysfunction.

Beraprost is used to treat peripheral chronic arterial occlusive disease. However, the efficacy and safety of beraprost in patients with pulmonary hypertension (PH) due to left ventricular systolic dysfunction (PH-HFrEF) remains unknown. The primary objective of this study was to determine the effects of beraprost on PH-HFrEF.We prospectively recruited patients with PH-HFrEF as determined by echocardiography and right cardiac catheterization. Beraprost sodium was given orally (1 μg/kg/d) added to the usual treatment, and patients were evaluated at 1-year follow-up.Twenty-five patients were recruited with baseline systolic pulmonary artery pressure (PAP) of 49.5 ± 10.8 mm Hg. Systolic PAP results at 3, 6, 9, and 12 months were 39.1 ± 8.1, 30.4 ± 5.2, 27.7 ± 3.0, and 27.0 ± 4.7 mm Hg, respectively, which were all significantly lower than systolic PAP at baseline (P < .05). Left ventricular ejection fraction results at 6 months (43.5 ± 7.0%), 9 months (47.0 ± 5.5%), and 12 months (48.2 ± 4.8%) were significantly higher than at baseline (34.7 ± 9.2%) (P < .05). Six-minute walking distance at 3 months (282.8 ± 80.6 m), 6 months (367.1 ± 81.2 m), 9 months (389.8 ± 87.1 m), and 12 months (395.7 ± 83.4 m) increased with time, and all were significantly higher than baseline (190.1 ± 75.5 m) (P < .05). One patient developed atrial fibrillation and recovered to sinus rhythm after intravenous administration of amiodarone. There were no instances of cardiac-related death, severe bleeding, or severe impairment of liver function.Routine oral administration of beraprost sodium added to the usual treatment may improve cardiopulmonary hemodynamics and exercise capacityin patients with PH-HFrEF.

Effect of beraprost sodium on pulmonary hypertension due to left ventricular systolic dysfunction: protocol for a randomized controlled clinical trial

Background and objectives: Beraprost sodium is mainly adapted to peripheral chronic arterial occlusive disease. However, the efficacy and safety of beraprost sodium in patients with pulmonary hypertension (PH) due to left ventricular systolic dysfunction (PH-HFrEF) remain unknown. The main objective of this study is to ascertain the efficacy and safety of beraprost sodium in the treatment of PH-HFrEF. Subjects and methods: In this prospective, multi-center, randomized, controlled clinical trial, 462 consecutively recruited patients with PH-HFrEF are randomly assigned to receive routine treatment only or routine treatment in combination with oral administration of beraprost sodium 1 μg/kg for 1 year. All patients are followed up at 3, 6, 9 and 12 months after treatment. Systolic pulmonary artery pressure and left ventricular ejection fraction are assessed by echocardiography, and exercise tolerance is assessed by a 6-minute walk test. Cardiac events are also recorded. This trial was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Soochow University (approval number: JD-LK-2017-021-02). Patient recruitment began in February 2018. Analysis of primary outcome measure will be completed in September 2021, and the study will be finished in September 2021. Outcome measures: Outcome measures are assessed at baseline and at 3, 6, 9 and 12 months after treatment. The primary outcome measure is the reduction rate of systolic pulmonary artery pressure. The secondary outcome measures are the incidence of major adverse cardiac events, left ventricular ejection fraction, and 6-minute walking distance. Discussion: Results of this study will provide evidence to validate whether application of beraprost sodium based on routine treatment can further reduce pulmonary artery pressure, improve cardiac function, reduce the incidence of heart events, and finally determine whether beraprost sodium is suitable for the treatment of PH-HFrEF. Trial registration: This trial was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-IPR-17012961) on October 12, 2017.

Effects of Oral Administration of Prostaglandin I2 as a Salvage Treatment in Patients with Sudden Deafness

We examined the effect of oral administration of beraprost sodium, a derivative of prostaglandin I2 (PGI2) in patients with sudden deafness as a salvage treatment after failure of initial systemic steroid therapy with prostaglandin E1. We then compared them with those of mecobalamin, a derivative of vitamin B12. A significant improvement in the average hearing level was obtained in patients who received beraprost sodium for 12 weeks, but not in patients who received mecobalamin. The hearing levels at 125 Hz, 250 Hz, 500 Hz and 8000 Hz significantly improved after the salvage treatment of beraprost sodium over those of mecobalamin. These findings suggested that oral administration of the PGI2 derivative could be utilized as a salvage treatment for refractory sudden deafness after failure of initial steroid therapy.

Effect of Beraprost Sodium in Patients with Chronic Obstructive Pulmonary Disease

Background : Pulmonary vascular changes which occur early in the course of chronic obstructive pulmonary disease (COPD) are prevalent manifestation and later cause pulmonary hypertension, which is a bad prognostic factor in COPD. Beraprost sodium (BPS), an orally active prostacyclin analogue, has been shown to improve survival in patients with primary pulmonary hypertension. This study investigated the effect of BPS in the patients with COPD. Methods : This is a double-blind randomized placebo-controlled, two center clinical trial. Twenty one consecutive patients with COPD were enrolled from June 2003 to June 2004 (patients treated with BPS for 3 months, BPS group, n=11; those with placebo, placebo group, n=10). The baseline demographic, pulmonary function and hemodynamic data were not significantly different between two groups. Results : On echocardiographic examination, trans tricuspid valve pressure gradient has decreased significantly after 3 months with beraprost in the BPS group [17.7(±11.4) to 8.2(±8.9) mm Hg, p-value<0.05], while there was no significant change in the control group. Six-minute walking distance has decreased in the control group and increased in the BPS group, but there was no statistical significance. Conclusion : In patients with COPD oral administration of BPS reduced the pulmonary arterial pressure. The clinical significance of this finding, that is improving symptoms and natural course of the disease, needs further study. (Tuberc Respir Dis 2004; 57:320-328)

Effect of Orally Active Prostacyclin Analogue on Survival in Patients With Chronic Thromboembolic Pulmonary Hypertension Without Major Vessel Obstruction

This study investigated whether treatment with beraprost sodium (BPS), an orally active prostacyclin analog, improves hemodynamics and survival in patients with peripheral-vessel chronic thromboembolic pulmonary hypertension (CTEPH), for which there is no surgical option. Oral administration of BPS has been shown to improve the hemodynamics and prognosis in patients with primary pulmonary hypertension; however, whether BPS has beneficial effects in CTEPH remains unknown. Forty-three patients with peripheral-vessel CTEPH were classified into two groups: patients treated with BPS (BPS group, n = 20) and those without BPS (conventional group, n = 23). Baseline demographic and hemodynamic data did not significantly differ between the two groups. BPS therapy improved New York Heart Association functional class in 10 patients (50%) and significantly decreased total pulmonary resistance from 18 +/- 6 to 15 +/- 8 Wood units (p < 0.05) [mean +/- SD]. Sixteen patients died of cardiopulmonary causes in the conventional group during a mean follow-up period of 58 +/- 45 months. In contrast, only three patients died of cardiopulmonary causes in the BPS group during a mean follow-up period of 44 +/- 30 months. The absence of BPS therapy, elevated total pulmonary resistance, heart rate, and age were independently related to the mortality by Cox proportional hazard analysis. The 1-year, 3-year, and 5-year survival rates for the BPS group were 100%, 85%, and 76%, respectively, compared to 87%, 60%, and 46% in the conventional group. This preliminary study suggests that oral administration of BPS may improve hemodynamics and survival in patients with peripheral-vessel CTEPH, for which there is no surgical option.

A stable prostacyclin analog, beraprost sodium, attenuates platelet accumulation and preservation-reperfusion injury of isografts in a rat model of lung transplantation.

Recent studies have shown that the extent of platelet accumulation in the vasculature of transplanted organs correlates with the degree of preservation-reperfusion injury. In this study, we examined the effect of a stable prostacyclin analog, beraprost sodium, which possesses potent antiplatelet activity, on parameters of platelet accumulation and preservation-reperfusion injury of isografts in a rat model of lung transplantation. The heart-lung blocks of donor rats were flushed with and preserved in modified Euro-Collins solution at 4 degrees C for 6 hr or 24 hr. The left lung was transplanted into recipient rats and reperfused for 1 hr. Lung injury was evaluated by the pulmonary blood flow ratios to the lung isografts, the weight gain of the isografts, and histological examination. Small portions of the lung isografts were excised and stained with an antibody specific for rat platelets. A scoring system was developed to semiquantitate the intensity of antibody staining (score 0-4). The recipient rats received oral administration of beraprost sodium (0.3 mg/kg) before lung transplantation. Control animals received no beraprost sodium. In the 6-hr preservation study, administration of beraprost sodium significantly reduced the score for platelet accumulation (1.8+/-0.4 vs. 3.3+/-0.5, P<0.01). This observation was accompanied by a significantly decreased degree of preservation-reperfusion injury as evidenced by an increased blood flow ratio (13.7+/-2.6% vs. 4.5+/-3.6%, P<0.01) and a reduced weight gain (0.7+/-0.2 g vs. 1.1+/-0.2 g, P<0.01). Histological examination revealed severe capillary congestion in three of six cases in the control group, while no capillary congestion was observed in the beraprost group. In the 24-hr preservation study, no differences were seen in platelet accumulation scores or parameters of lung injury. Beraprost sodium, an antiplatelet agent, reduces platelet accumulation and preservation-reperfusion injury of lung transplants at 6 hr in this rat isograft model.

Acute effect of beraprost sodium on lower limb circulation in patients with non-insulin-dependent diabetes mellitus-evaluation by color doppler ultrasonography and laser cutaneous blood flowmetry

The acute effects of beraprost sodium (sodium (±)-(1R ∗, 2R, 3aS ∗, 8bS ∗)-2, 3, 3a 8b-tetrahydro-2-hydroxy-l-((E)-(3S ∗)-3-hydroxy-4-methylI-octen-6-yny1] -1H-cyclopenta [b] bensofuran-5-butyrate), a stable analogue of prostaglandin I 2 which works as a vasodilator and anti-platelet agent, were investigated in patients with non-insulin dependent diabetes mellitus. Its effects on the dorsal pedis artery were examined using a new real-time two-dimensional Doppler ultrasonographic technique and by laser blood flowmetry. Before and 60 min after oral administration of beraprost sodium (Dolner ® 40 μg) and elastase (Elaszym ® 1800 U), the cross-sectional area (CSA) of the dorsal pedis artery and its blood flow index (BFI), calculated from the maximum flow velocity and area, were determined. Dermal microcirculatory blood volume (MBV) was also measured by laser blood flowmetry. In the beraprost sodium group, the CSA, BFI and MBV were significantly increased, while in the elastase group, no significant changes were observed. These result suggest that beraprost sodium has a beneficial effect on diabetic macro- and microangiopathy.

Prevention of abnormalities in motor nerve conduction and nerve blood-flow by a prostacyclin analog, beraprost sodium, in streptozotocin-induced diabetic rats

The effects of the prostacyclin analog beraprost sodium on motor nerve function and nerve blood-flow were examined in streptozotocin-induced diabetic rats. Oral administration of beraprost sodium 0.1 mg/kg/day for 8 wks significantly ( P < 0.001) improved caudal motor nerve conduction velocity and sciatic nerve blood-flow, both of which are impaired in diabetic rats. Beraprost sodium did not affect glucose, sorbitol, or fructose levels in the sciatic nerve. However, a decreased content of cyclic AMP in the sciatic nerve and higher level of thromboxane B 2 in the thoracic aorta of diabetic rats, as compared with those in normal rats, were reversed by the treatment with beraprost sodium ( P < 0.01). Results suggest that beraprost sodium may have value in treating diabetic neuropathy, mainly by improving endoneurial blood-flow.

Platelet antiaggregating effects of acute and repeated oral administration of beraprost sodium in healthy volunteers

Platelet antiaggregating effects of acute and repeated oral administration of beraprost sodium in healthy volunteers

経口ｐｒｏｓｔａｃｙｃｌｉｎ誘導体ｂｅｒａｐｒｏｓｔ ｓｏｄｉｕｍ（ＴＲＫ‐１００）の第Ｉ相臨床試験 単回投与試験

A phase I study by single oral administration of beraprost sodium (TRK-100), a prostacyclin derivative, was performed in 32 healthy male volunteers. The safety, pharmaco-kinetics, and pharmacological effects were studied in two single oral administration clinical trials.Study 1 was performed in 12 volunteers to investigate the safety and pharmacokinetics of TRK-100. The 12 men received 50, 100, and 200 μg of TRK-100 at intervals of two wk.Study 2 was performed in 20 volunteers, randomly divided into three groups, to investigate the pharmacological effects and safety of TRK-100 at the dose of 25, 50, and 100μg. The results were as follows:1) Subjective symptoms: Facial flushing, feeling of congestion, dull headache, headache, and sleepiness, etc., appeared in some subjects. These symptoms were observed more frequently in the groups receiving 100 and 200μg. Almost all symptoms disappeared within 2 or 3 hr after administration.2) Physical and laboratory tests: Plasma calcification time and prothrombin time were prolonged slightly. But no abnormality was observed in other test items.3) Pharmacokinetics: Following a single oral administration of 100 and 200μg, Cmax was twice as high in the group receiving 200μg as in the group receiving 100μg. Tmax was 1. 42 hr in the group receiving 100μg and 1.07 hr in the group receiving 200μg. T1/2 was 1.11 hr and 0.89 hr, respectively.4) Pharmacological effect: TRK-100 inhibited platelet aggregation induced by ADP, collagen, and epinephrine dose-dependently.The above results indicated the safety and pharmacological effects of TRK-100 in single oral administration in healthy male volunteers.