STUDY OBJECTIVES We report on the long-term safety and efficacy of bosentan treatment in patients with pulmonary arterial hypertension (PAH). BACKGROUND In a preceding study, bosentan was well tolerated and significantly improved the exercise capacity and hemodynamics of patients with PAH after 12 weeks of treatment. DESIGN The present study was an open-label extension to the preceding doub...

BACKGROUND Hepatotoxicity is a major side effect of treatment with bosentan in patients with pulmonary hypertension (PH). Bosentan is metabolized by the cytochrome CYP2C9 and inhibits the bile salt export pump, which is encoded by ABCB11. This suggests that genetic variants of CYP2C9 and/or ABCB11 may predispose patients to bosentan-induced liver injury. MATERIAL AND METHODS PH patients with ...

Idiopathic pulmonary fibrosis (IPF) is a fatal disease for which no effective treatment exists. In the present study, 12 IPF patients underwent analysis of gas exchange properties using the multiple inert gas elimination technique on day 1 before and after the administration of 125 mg bosentan, a dual endothelin antagonist. Following this, patients received chronic administration for 12 weeks (...

Pulmonary arterial hypertension (PAH) still cannot be cured, warranting the search for novel treatments. Fasudil (a Rho kinase inhibitor) was compared with bosentan (an endothelin receptor blocker) and sildenafil (a phosphodiesterase 5 inhibitor), with emphasis on right ventricular (RV) function, in a reversal rat model of monocrotaline (MCT)-induced PAH. In addition, the effects of combining b...

OBJECTIVES In this study, we performed a systematic review and meta-analysis of oral bosentan in adult congenital heart disease associated pulmonary arterial hypertension (CHD-PAH) to evaluate its safety and tolerability. MATERIALS AND METHODS Online electronic database including PubMed, EMBASE and Springer were searched from October 2006 to October 2013 to collect the clinical studies or coh...

OBJECTIVE: In order to provide an overview of current knowledge, the literature was systematically examined for clinical studies, which evaluate the safety and effectiveness of bosentan in pediatric pulmonary arterial hypertension (PAH). SOURCES: 3 databases (MEDLINE, EMBASE and BIOSIS) were searched for the period January 2000 October 2007 using the key words 'pulmonary arterial hypertension',...

INTRODUCTION Pulmonary arterial hypertension is a fatal disease characterized by progressive remodeling of the pulmonary arteries and an increase in pulmonary vascular resistance. Up to 50% of patients with systemic sclerosis have pulmonary arterial hypertension, which significantly affects the prognosis. The endothelin receptor antagonist bosentan is used for the treatment of pulmonary arteria...

OBJECTIVE Importance of endothelin in mediating the chronic renal alterations of chronic heart failure was studied in rats chronically treated with bosentan after myocardial infarction. METHODS Rats were subjected to coronary artery ligation and were treated for 8 weeks with placebo or bosentan, a dual ET(A) and ET(B) receptor antagonist, (approximately 100 mg/kg/day) as food admix. Sham-oper...

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK2...

In this study, simple, fast and reliable cyclic voltammetry (CV), linear sweep voltammetry (LSV), square wave voltammetry (SWV) and differential pulse voltammetry (DPV) methods were developed and validated for determination of bosentan in pharmaceutical preparations. The proposed methods were based on electrochemical oxidation of bosentan at platinum electrode in acetonitrile solution containin...