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Introduction: Quantitative information on disposition of maternal medicines in human milk remains a major knowledge gap. This case report presents the clinical and pharmacokinetic data of a single mother-infant pair exposed to bosentan and sildenafil for the treatment of pulmonary arterial hypertension (PAH) during lactation.Case presentation: A 43-year old mother was treated with sildenafil (20 mg, 3x/day) and bosentan (125 mg, 2x/day) for PAH. Her 21-months old infant received breastfeeding in combination with adequate complementary foods. Milk samples were collected over 24 h, at day 637 and 651 after delivery. The observed average steady-state concentrations of sildenafil (2.84 μg/L) and bosentan (49.0 μg/L) in human milk were low. The Daily Infant Dosage ingested by the nursing infant through human milk was 0.02 μg/kg/day for sildenafil and 0.29 μg/kg/day for bosentan at day 637, and 0.03 μg/kg/day and 0.60 μg/kg/day at day 651. The Relative Infant Dose calculated for an exclusively breastfed infant with an estimated milk intake of 150 ml/kg/day, was 0.06% for sildenafil and 0.24% for bosentan. General health outcome of the infant, reported by the mother, was uneventful until the sampling days.Conclusion: Low medicine concentrations were found in human milk expressed 21 months after delivery after maternal intake of 20 mg sildenafil three times daily and 125 mg bosentan twice daily. General health of the nursing infant until sampling was reported as optimal by the mother.

Abstract Even though pulmonary arterial hypertension (PAH) remains an incurable disease, the combination of PAH‐specific therapies allowed treatment strategies to evolve from symptom‐based ones to others that aim to move patients to low‐risk conditions. Endothelin‐1 (ET‐1) receptor antagonists emerged as specific‐PAH drugs that can be used in combination with other specific therapies. This work aimed to perform a prospective clinical assessment of patients with PAH that switched from bosentan to macitentan (POTENT), due to inadequate response. POTENT is a prospective, open‐label, single‐arm, uncontrolled study including PAH patients from our ongoing SAUDIPH registry. It enrolled 50 PAH patients divided as follows: idiopathic/heritable pulmonary arterial hypertension (I/HPAH); n = 24; PAH associated with congenital heart disease, n = 19; PAH associated with connective tissue diseases, n = 5; and pulmonary veno‐occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH), n = 2. At baseline, most patients were in World Health Organization Functional Class (WHO FC) II/III (52.0%). After switching to macitentan, patients were more likely to be in WHO FC I/II (78%) and 22% of the overall cohort moved to a lower risk condition, with three low risk stratification parameters. Mean 6‐min walking distance increased about 34 m after 12 months, with a significant mean change over time (12.63 ± 11.69 at month 3 vs. 40.75 ± 12.57 at month 12, p = 0.002). Most haemodynamic parameters decreased over time, with corresponding negative mean changes (p

Endothelin-1 (ET-1) has been implicated in the pathogenesis of cardiac fibrosis. Stimulation of endothelin receptors (ETR) with ET-1 leads to fibroblast activation and myofibroblast differentiation, which is mainly characterized by an overexpression of α-smooth muscle actin (α-SMA) and collagens. Although ET-1 is a potent profibrotic mediator, the signal transductions and subtype specificity of ETR contributing to cell proliferation, as well as α-SMA and collagen I synthesis in human cardiac fibroblasts are not well clarified. This study aimed to evaluate the subtype specificity and signal transduction of ETR on fibroblast activation and myofibroblast differentiation. Treatment with ET-1 induced fibroblast proliferation, and synthesis of myofibroblast markers, α-SMA, and collagen I through the ETAR subtype. Inhibition of Gαq protein, not Gαi or Gβγ, inhibited these effects of ET-1, indicating the essential role of Gαq protein-mediated ETAR signaling. In addition, ERK1/2 was required for ETAR/Gαq axis-induced proliferative capacity and overexpression of these myofibroblast markers. Antagonism of ETR with ETR antagonists (ERAs), ambrisentan and bosentan, inhibited ET-1-induced cell proliferation and synthesis of α-SMA and collagen I. Furthermore, ambrisentan and bosentan promoted the reversal of myofibroblasts after day 3 of treatment, with loss of proliferative ability and a reduction in α-SMA synthesis, confirming the restorative effects of ERAs. This novel work reports on the ETAR/Gαq/ERK signaling pathway for ET-1 actions and blockade of ETR signaling with ERAs, representing a promising therapeutic strategy for prevention and restoration of ET-1-induced cardiac fibrosis.

Materials and Methods: The aim of the present systematic review and meta-analysis was to evaluate the therapeutic efficacy of bosentan, a dual endothelin receptor antagonist, for systemic sclerosis (SSc) patients with digital ulcers (DUs). Methods: A systematic search of MEDLINE, Embase, Web of Science, and Scopus was done using appropriate keywords till September 2021. Weighted mean difference (WMD) as the effect of therapeutic efficacy of bosentan on continuous outcomes was an estimate. Furthermore, the pooled prevalence of diffuse SSc and limited SSc was computed. Fixed or random effects models when appropriate were used for data synthesis. Results: Totally, 469 patients, with a mean age ranging from 48.1 to 63.7 years, from 8 studies were included in the systematic review and meta-analysis. The pooled frequency of diffuse SSc and limited SSc was 56% (95% confidence interval [CI]: 39%, 73%) and 44% (95% CI: 27%, 61%). The pooled prevalence of new DUs following bosentan treatment was 21% (95% CI: 10%, 33%). The results of the meta-analysis showed a pooled mean decrease of WMD: −0.09 (95% CI: −0.020, 0.02, P= 0.10), WMD: −2.82 (95% CI: −5.91, 0.27, P= 0.07), and WMD: −6.65 (95% CI: −9.49, −3.82, P< 0.001) in mean SSc-Health Assessment Questionnaire, pain, and Rodnan score, respectively. Our meta-analysis also indicated a significant pooled decrease in the number of new DUs in SSc patients compared to placebo subjects (WMD: −0.89 [95% CI: −1.40, −0.37; P= 0.001]) and baseline values (WMD: −1.34 (95% CI: −1.95, −0.73; P< 0.001). Conclusion: Bosentan possibly is an efficacious treatment option for SSc-related DUs. Although further large-scale randomized clinical trials are required to confirm the preliminary finding and underlying mechanisms of action.

Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Al-Mustansiriyah Journal for Pharmaceutical Sciences is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Obesity is associated with dysregulation of the endothelin system. In individuals with obesity, an exaggerated pressor response to acute stress is accompanied by increased circulating endothelin-1 (ET-1). The impact of combined endothelin A/B receptor (ETA/B) antagonism on the stress-induced pressor response in overweight/obese (OB) individuals is unknown. The objective of this study is to test the hypothesis that treatment with an ETA/B antagonist (bosentan) would reduce the stress-induced pressor response and arterial stiffness in overweight/obese compared with normal weight (NW) individuals. Forty participants [normal weight (NW): n = 20, body mass index (BMI): 21.7 ± 2.4 kg/m² and overweight/obese (OB): n = 20, BMI: 33.8 ± 8.2 kg/m² ] were randomized to placebo or 125 mg of bosentan twice a day (250 mg total) for 3 days. Hemodynamics were assessed before, during, and after a cold pressor test (CPT). Endothelin-1 was assessed at baseline and immediately after CPT. Following a washout period, the same protocol was repeated with the opposite treatment. The change from baseline in mean arterial pressure (MAP) during CPT following bosentan was significantly lower (P = 0.039) in the OB group than in the NW group (OB: 28 ± 12 vs. NW: 34 ± 15 mmHg). These results suggest that ETA/B antagonism favorably blunts the pressor response to acute stress in overweight/obese individuals. [ABSTRACT FROM AUTHOR]

Inhaled nitric oxide (iNO) is approved for use in persistent pulmonary hypertension of the newborn (PPHN) but does not lead to sustained improvement in oxygenation in one-third of patients with PPHN. Inhaled NO is less effective in the management of PPHN secondary to congenital diaphragmatic hernia (CDH), extreme prematurity, and bronchopulmonary dysplasia (BPD). Intravenous pulmonary vasodilators such as prostacyclin, alprostadil, sildenafil, and milrinone have been successfully used in PPHN resistant to iNO. Oral pulmonary vasodilators such as endothelin receptor antagonist bosentan and phosphodiesterase-5 inhibitors such as sildenafil and tadalafil are used both during acute and chronic phases of PPHN. In the absence of infection, glucocorticoids may also be effective in PPHN. Many of these pharmacologic agents are not approved for use in PPHN and our knowledge is based on case reports and small trials. Large multicenter randomized controlled trials with long-term follow-up are required to evaluate alternate pharmacologic strategies in PPHN.

Purpose: To study the efficacy of bosentan combined with sildenafil in the treatment of severe pulmonary hypertension (PH), and its impact on cardiac function. Methods: In total, 90 severe PH patients treated in The First Affiliated Hospital of Harbin Medical University, Harbin, China between November 2018 and November 2019 were included and equally assigned to two groups (A and B). Group A was treated with bosentan combined with sildenafil, while group B received conventional treatment, viz, deslanoside injection followed later by 40 mg furosemide intravenous injection. Clinical efficacy, sleep quality, psychological status, and cardiac function for the two groups were compared. Results: Group A had significantly higher effectiveness than group B before treatment (p < 0.05). Similar Pittsburgh Sleep Quality Index (PSQI) scores before treatment between the two groups were found (p > 0.05). After treatment, group A had a lower PSQI score than group B (p < 0.001). Also, following treatment, group A had more level I patients and fewer level III patients than group B (p < 0.05). The Beck depression rating scale (BDI) scores at T0 and T1 were similar for the two groups (p > 0.05). Lower post-treatment BDI scores in group A at T2 and T3, than in group B were observed (p < 0.001). In contrast to the conventional treatment group, group A had a higher cardiac output and higher cardiac index, lower systemic arterial pressure, and lower incidence of adverse reactions (p < 0.05). Conclusion: Bosentan combined with sildenafil produces higher therapeutic effects on severe PH patients than conventional treatment. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Some patients present with excessive pulmonary hypertension (PH) prior to pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). This study was performed to evaluate the clinical role of pretreatment before PEA in CTEPH patients. METHODS A total of 370 patients with CTEPH undergoing first PEA between 2003 and 2017 were divided into those receiving pretreatment with bosentan (group B: n  =   119) and those without targeted pretreatment for PH (group C: n  =   251). After selecting patients given bosentan (2–8 months) and using propensity score matching, comparable patient cohorts (n  =   23 each) were created from both groups. PEA was performed in the standard manner, and the median number of extracted segments was 14. RESULTS There were no significant differences in perioperative demographic characteristics or 30-day mortality (overall 5.7%) between the groups before and after matching. In patients with preoperative pulmonary vascular resistance (PVR) ≥800 dynes s/cm5, a significantly larger decrease in PVR was found in group B (78%) compared to group C (68%) (P  =   0.033). There was no significant difference in late survival between the groups after matching. The frequency of residual/persistent PH (mean pulmonary artery pressure >25 mmHg) was lower in group B than in group C, although the difference was not significant (22% vs 39%, respectively, P  =   0.200). Advanced age and longer cardiopulmonary bypass time were independent predictors of both 30-day mortality and residual/persistent PH (odds ratio: age, 1.053, 1.013, cardiopulmonary bypass time, 1.065, 1.010, respectively). CONCLUSIONS Preoperative treatment of CTEPH patients with bosentan for 2–8 months can improve post-PEA PVR without adverse clinical events in patients with a high preoperative PVR. A temporary bridging regime appears beneficial in selected patients prior to PEA. [ABSTRACT FROM AUTHOR]

Although there are rapid developments in molecular science and synthetic chemistry for investigation of many essential drug molecules, poor solubility and bioavailability issues are major constraint in the design of more efficient formulations. This research study focuses on the enhancement of solubility and development of the bucco-adhesive drug delivery system of bosentan using Soluplus® (polyvinyl-caprolactam-polyvinyl-acetate-polyethylene glycol graft co-polymer) as a carrier. A 32-factorial design was implemented to develop bucco-adhesive tablets using hydroxypropyl methyl cellulose (HPMC) K100 LV (X1) and Carbopol 934 P (X2) as independent variables at various levels whereas t50%(Y1) (time required to release 50% of drug), Rel4h (Y2) (percentage of the drug release in 4 h) and bio-adhesive strength (Y3) were considered as set response parameters. The positive effect of the surface response quadratic model demonstrated the change in the already set dependent variables of t50%, Rel4h and bio-adhesive strength. The FT-IR study confirmed the suitability of all the components used in the design of formulation. DSC and XRD study have confirmed the encapsulation of bosentan in the Soluplus® carrier and amorphous form of bosentan, respectively. Overall, 6.832-fold increase in solubility was observed for bosentan-solid dispersion. High-water uptake and swelling of bucco-adhesive tablets (containing bosentan-solid dispersion) was observed due to presence of the highly hydrophilic-Soluplus®. Rel4hwas found to be 97.86 ± 0.57% for optimized formulation (F4) and was decreased with increasing polymer content. The values of t50% were found to be enhanced from 1.11 to 2.32 h at the lower to higher levels of both the polymers respectively. [ABSTRACT FROM AUTHOR]

Abstract is missing (Short communication)

Introduction/objective: Coronavirus disease 2019 (COVID-19) has been the biggest pandemic in history, with severe complications, such as acute respiratory distress syndrome and pulmonary hypertension (PH). An endothelin-1 (ET-1) receptor antagonist, such as bosentan, may be beneficial in treating elevated ET-1 levels. Hence, our study aimed to evaluate the therapeutic effects of bosentan in patients with COVID-19-induced PH., Methods: A single-centre, randomized, double-blind study involving 72 participants was carried out; 36 received bosentan and the other 36 received a placebo. Pulmonary arterial pressure, tricuspid valve pressure gradient, and right atrial pressure were measured using echocardiography. The Cox proportional hazards regression model was used to investigate the impact of bosentan and patients' age on mortality during a 6-month follow-up period., Results: In-hospital mortality was significantly lower in the case group (13%) compared with the control group (33.3%) (P=0.003). Additionally, bosentan improved echocardiographic parameters, such as systolic pulmonary artery pressure and tricuspid regurgitation gradient (P=0.011 and P=0.003, respectively). Bosentan use was a significant predictor of long-term mortality rates for 600 days [age-adjusted hazard ratio of 5.24 (95% CI 1.34 to 20.46)]., Conclusion: This study provided a mixed perspective on the use of bosentan therapy in patients with COVID-19-related PH. Bosentan effectively reduced in-hospital mortality and improved echocardiographic measures. However, the treatment group showed an increased requirement for supplemental oxygen therapy and long-term mortality. Further studies with larger sample sizes are necessary to elucidate the effects of bosentan in PH following COVID-19., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Persistent Pulmonary Hypertension of the newborn (PPHN) is characterized by sustained elevated Pulmonary Artery Pressure (PAP). Drug resistance and the adverse effects of current therapeutic agents warrant investigation of other targeted therapies. Bosentan has shown benefits in affected neonates. However, trials reported the association with unwanted effects. Thus, in this study, we assess another agent in the same family, Macitentan. However, its efficacy in the treatment of PPHN is not yet reported. Hence, this study evaluated the effect of Macitentan compared to Bosentan in terms of efficacy and safety in the treatment of PPHN., Methods: This randomized, double-blinded non-inferiority clinical trial was conducted in Shahid Akbar Abadi hospital, Tehran, Iran. Sixty clinically stable neonates with signs suggestive of PPHN were randomly allocated into two groups (n = 30 in each group) and they received either Bosentan 1 mg/kg/dose BD (twice daily) or Macitentan 1 mg/kg/dose BD simultaneously with sildenafil. The echocardiographic and laboratory indices of efficacy and safety were compared between groups. SPAP (systolic pulmonary artery pressure) was used to assess the non-inferiority of the Macitentan compared to the Bosentan in their respective doses used in the study., Results: Participants' mean (SD) age was 3.53 (1.21) days, and 55% were female. No mortality case occurred. SPAP was reduced in both Bosentan and Macitenan groups with the mean difference in SPAP of 9 (95% CI: 7.34-10.65) in Bosentan and SPAP mean difference of 14 (95% CI: 12.12-15.86) in Macitentan group. Categorical comparison of primary outcome improvement showed that Macitentan was superior to Bosentan with a 10% non-inferiority margin. Similar results were obtained in other echocardiographic indices. Also, no significant alterations were observed in laboratory safety parameters., Conclusion: Macitentan 1 mg/kg/dose BD (twice daily) is non-inferior to Bosentan 1 mg/kg/dose BD in improving echo outcomes of PPHN and it was even more effective in improving some of these. Also, it is non-inferior to Bosentan in terms of safety. TRIAL REGISTRY NUMBER: (IRCT20160120026115N9)., Competing Interests: Declaration of competing interest The authors have no competing interests., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

The objective of our study was to contribute to the characterization of monocrotaline-induced pulmonary arterial hypertension (PAH) in a rat model, with emphasis on the renin–angiotensin–aldosterone system, parameters of oxidative stress, the activity of matrix metalloproteinases, and erythrocyte parameters. Moreover, we aimed to analyze the effects of bosentan. Experiments were performed on 12-week-old male Wistar rats randomly assigned to 3 groups: control, monocrotaline-treated (60 mg/kg), and monocrotaline combined with bosentan (300 mg/kg/day). Our study confirmed the well-known effects of monocrotaline administration on lungs and the right ventricle, as well as pulmonary arterial pressure. In addition, we observed activation of the alternative pathway of the renin–angiotensin system, namely an increase in angiotensin (Ang) 1–7 and Ang 1-5 together with an increase in Ang I, but without any change in Ang II level, and downregulation of aldosterone 4 weeks after monocrotaline administration. For the first time, modifications of erythrocyte Na,K-ATPase enzyme kinetics were demonstrated as well. Our observations do not support data obtained in PAH patients showing an increase in Ang II levels, increase in oxidative stress, and deterioration in RBC deformability. Although bosentan primarily targets the vascular smooth muscle, our study confirmed its antioxidant effect. The obtained data suggest that besides the known action of bosentan, it decreases heart rate and increases erythrocyte deformability, and hence could have a beneficial hemodynamic effect in the PAH condition.

Background: In order to measure the plasma levels of Losartan and Bosentan, a sensitive Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) technique was developed., Methods: To compare bioavailability, the Area Under the Curve (AUC), peak plasma concentration (Cmax), and time to Cmax (Tmax) were employed. The standard curve (150-2400 ng/ml ) was linear (R 2 =0.999), relative errors were between 2.4 to 10.05% and the coefficient of variation (CV%) ranged from 1.52 to 10.88. A single dosage (test and reference) was used for the in vivo investigation, which involved 16 healthy individuals., Results: The AUC0-48, AUC0-, Cmax, and Tmax of the test and reference had no statistically significant differences. The C max and 95% confidence intervals of the ratio of C max of the two formulations were 0.93-0.96 and 97.6-135%, respectively., Conclusion: Therefore, it was established that generic Bosentan was equivalent to Bosentan from Actelion and that both medications could be regarded as equally effective in clinical settings. The blood level of Bosentan could be measured using this straightforward procedure in all hospital laboratories., (Copyright© 2024 Avicenna Research Institute.)

Objective(s): We examined the antiosteoporotic effect of bosentan (Bose) by radiographic, histopathological, and molecular methods. Materials and Methods: Rats were divided into 4 groups of 8 rats each: one control (Sham), one osteoporosis only (OP), and two osteoporosis groups treated with Bose doses of 50 and 100 mg/kg (OP+Bose50, OP+Bose100). Six weeks later, Bose was administered for eight weeks to animals undergoing ovariectomy. The left femoral bone of the rats was evaluated in vitro after surgical removal. Bone mineral density (BMD) was analyzed by Dual-energy X-ray absorptiometry (DEXA). Endothelin 1 (ET-1), ET-A, and ET-B expressions were examined by real-time polymerase chain reaction (real time-PCR). In addition, bone tissue was evaluated histopathologically. Results: Compared with the osteoporosıs group, Bose significantly increased BMD values at both 50 and 100 mg/kg doses. ET-1 mRNA levels were significantly higher in the OP group than in the Sham group, while ET-1 mRNA levels were significantly lower in Bose treatment groups. ET-A mRNA levels were significantly lower in the OP group than in the Sham group, while ET-A mRNA levels were significantly higher in Bose treatment groups. Histopathological results supported the molecular results. Conclusion: Our study is the first to demonstrate the molecular, radiological, and histopathological effects of Bose in preventing osteoporosis in rats. [ABSTRACT FROM AUTHOR]

Eisenmenger syndrome (ES) refers to congenital heart diseases (CHD) with reversal flow associated with increased pulmonary pressure and irreversible pulmonary vascular remodeling. Previous reports showed limited therapeutic strategies in ES. In this study, 5 ES patients (2 males and 3 females), who had been followed regularly at our institution from 2010 to 2019, were retrospectively reviewed. We adopted an add-on combination of sildenafil, bosentan, and iloprost and collected the clinical characteristics and outcomes as well as findings of echocardiography, computed tomography, pulmonary perfusion-ventilation scans, positron emission tomography, and biomarkers. The age of diagnosis in these ES patients ranged from 23 to 54 years (38.2 ± 11.1 years; mean ± standard deviation), and they were followed for 7 to 17 years. Their mean pulmonary arterial pressure and pulmonary vascular resistance index were 56.4 ± 11.3 mmHg and 24.7 ± 8.5 WU.m2, respectively. Intrapulmonary arterial thrombosis was found in 4 patients, ischemic stroke was noted in 2 patients, and increased glucose uptake of the right ventricle was observed in 4 patients. No patient mortality was seen within 5 years of follow-up. Subsequently, 2 patients died of right ventricular failure, 1 died of sepsis related to brain abscess, and another died of sudden death. The life span of these patients was 44–62 years. Although these patients showed longer survival, the beneficial data on specific-target pharmacologic interventions in ES is still preliminary. Thus, larger trials are warranted, and the study of cardiac remodeling in ES from various CHD should be explored.

Pulmonary artery hypertension (PAH) is a common and serious disease which is characterized by pulmonary vascular remodeling. Bosentan (BST) is the first approved oral targeted drug of endothelin-1 (ET-1) receptor antagonists for the treatment of PAH. MicroRNA-27a (miR-27a) and peroxisome proliferator-activated receptor γ (PPARγ) were found to be related to the pathogenesis of PAH. To further explore the signal transduction mechanism of BST in the treatment of PAH, we examined the effects of BST on endothelin receptors, miR-27a, and PPARγ. Meanwhile, the influence of miR-27a in the formation and development of PAH was discussed. Our results demonstrated that during the pathophysiology of PAH, miR-27a, PPARγ, and ET-1 were cross-inhibited, which indicated that the miR-27a/PPARγ/ET-1 signaling pathway was dysregulated; in addition, BST could competitively bind to ET-1 receptors and inhibit the miR-27a/PPARγ/ET-1 signaling pathway, thereby delaying the proliferation of PASMCs and affecting the development of PAH. Our results give a new understanding of the pathogenesis and treatment of PAH and provide more reliable evidence for the application of BST in the treatment of PAH in the clinic. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension patients experienced a high financial burden due to the high cost of drug therapy, high incidence of comorbidities and hospitalizations. Endothelin receptor antagonists (ERAs) in PAH treatment showed a high cost. While ambrisentan has been covered by medical insurance of a local government of China, there has been a drug transition from bosentan to ambrisentan in treating PAH patients. We evaluated the safety, efficacy and tolerability of ambrisentan after drug transition. Methods: Liver and renal functions were inspected at baseline, month 1, 3 and 6. NT-proBNP, echocardiographic variables, WHO functional class (WHO-FC), 6-minute walking distance (6MWD) were measured in the baseline and month 6 to evaluate the safety and efficacy. Quality of life (QOL) scale was used in the baseline and month 6 to investigate the tolerability and quality of life of PAH patients. Results: Among 224 PAH patients, 49 stable PAH patients meet the inclusion criteria were enrolled, among which three patients discontinued during the study. Our results showed no difference in 6-minute walking distance (6MWD) of PAH patients from baseline and month 6. The liver and renal function, N-terminal pro-brain natriuretic peptide (NT-proBNP), WHO functional class (WHO-FC) showed no difference either. For echocardiography parameters, the left ventricular end-diastolic dimension (LVEDD) of month 6 decreased. Other parameters were no significant difference from the baseline. There was no difference in the QOL scale between baseline and month 6. Conclusion: Our results suggested that it is safe and tolerable for stable PAH patients to transition from bosentan to ambrisentan without influencing hematologic parameters or heart function. [ABSTRACT FROM AUTHOR]