Background: Endothelin (ET)-1 has a pathogenic role in pulmonary arterial hypertension (PAH). Recent clinical studies carried out in Western populations showed that blockade of the ET receptors by bosentan improves pulmonary hemodynamics and exercise capacity. In the present study, the efficacy of bosentan was assessed in Japanese patients with PAH.
Method and results: Because the pharmacokinetics of bosentan and its metabolites are similar in Japanese and Caucasian subjects, the same dose of bosentan, 125 mg twice daily, was administered in the Japanese open-label clinical trial. In 18 patients, mean pulmonary arterial pressure decreased from 52.4+/-13.8 to 46.8+/-13.8 mmHg (p=0.003) and cardiac index increased from 2.20+/-0.74 to 2.61 +/-0.72 L.min(-1).m(-2) (p=0.002). The 6-min walking distance increased from 410+/-89.5 to 494+/-86.0 m (p<0.0001). The dyspnea index (Borg scale) decreased from 3.2+/-2.4 to 2.2+/-1.7 (p=0.02). The specific activity scale (SAS) gradually increased throughout the study period from 2.9+/-0.8 to 4.6+/-1.9 METs (p=0.0005). WHO Class improved in 10 patients.
Conclusion: Bosentan was well tolerated and improved the hemodynamics, symptoms, exercise capacity, and quality of life of Japanese patients with PAH. Thus, bosentan can be a valuable therapeutic option in Japanese patients.