title: Effects of the endothelin receptor antagonist bosentan on hemodynamics, symptoms and functional capacity in Japanese patients with severe pulmonary hypertension.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hamamatsu Rosai Hospital, Japan.
authors.forename: Shigetake
authors.initials: S
authors.lastname: Sasayama
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Kunieda
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: Kunio
authors.initials: K
authors.lastname: Shirato
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuriyama
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
authors.forename: Hideki
authors.initials: H
authors.lastname: Origasa
authors.forename: Paul Lm van
authors.initials: PL
authors.lastname: Giersbergen
authors.forename: Jasper
authors.initials: J
authors.lastname: Dingemanse
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D044466:Asian People; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D002302:Cardiac Output / Q000187:drug effects; D004417:Dyspnea; D065128:Endothelin Receptor Antagonists; D005080:Exercise Test / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000208:ethnology / Q000503:physiopathology; D010599:Pharmacokinetics; D011788:Quality of Life; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D044465:White People
chemical_list: D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan