【文　摘】瑞士Actelion公司的Tracleer(bosentan，波生坦)(I)可与ETa和ETb受体结合，是一种内皮素双受体拮抗剂，是唯一被批准用于治疗肺动脉高压的口服药物。已经有证据表明，它可改善患者的症状及临床进程，同时提高患者的长期生存率。2001年11月在美国首次上市以来，其表现远远超过了预期的市场效果。
      
欧洲批准肺动脉高压治疗药Tracleer 用于儿童
Actelion公司药品Tracleer已在欧洲获准用于儿童患者，该药用于治疗肺动脉高压（PAH）。该公司表示，此次获准之后，Tracleer成为唯一可用于2岁以上儿童患者的PAH药物。PAH对于患儿来说是一种重症疾病，若在确诊后不加以治疗，他们的中位生存期仅为10个月。
Actelion公司药物研发负责人Martine Clozel表示：“尽管儿童PAH患者人数极少，但在开发Tracleer之初，我们就注重研究可用于治疗这类患者的配方。这种32毫克的分散片根据儿童低体重的特点专门配制，使用起来方便、剂量精确、也更为灵活。此外，研究结果发现，儿童患者用药后，安全性及耐受性和成人患者相当。”
日内瓦Enfants医院儿科心脏病专家Maurice Beghetti也提到，Actelion在欧洲获准治疗儿童PAH患者令人欣喜，这开启了一个以精确药用剂量治疗这类患者的先河。
2008年，Tracleer的销售额达到12.9亿瑞士法郎，比2007年增长10%。目前，Actelion公司也正在研究该药治疗特发性肺纤维化的效果。

Bosentan (Tracleer®) About bosentan in clinical developmentBosentan (Tracleer®), is an oral dual endothelin receptor antagonist, which is currently approved for the treatment of PAH, a chronic, life-threatening disorder which severely compromises the function of the lungs and heart. In the United States, Tracleer is approved for treatment of PAH Functional Class III and IV to improve exercise capacity and decrease the rate of clinical worsening, and in the European Union (EU) it
is approved for treatment of PAH Functional Class III to improve exercise capacity and symptoms, as well as PAH Functional Class II where some improvements have also been shown. In the EU, Tracleer® is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease.
Actelion’s development efforts for bosentan concentrate on compiling evidence in PAH sub-populations to assist doctors in their treatment approach. In addition, Actelion’s development team is actively investigating bosentan’s potential in other endothelin-related diseases.
Building on our knowledge about the effects of elevated endothelin levels, we are developing bosentan beyond PAH and digital ulcers as a treatment for idiopathic pulmonary fibrosis (IPF). IPF is a progressive and usually fatal disease of the lungs for which, for patients outside Japan, there is currently no approved therapy.
       
Bosentan in combination with sildenafil
Current status
The COMPASS program specifically evaluates safety and efficacy of the use of bosentan in combination with sildenafil. Sildenafil is an approved treatment for PAH but one which works by its effect on another pathological pathway of the disease.
Actelion has concluded COMPASS-1, the first clinical trial to provide detailed hemodynamic information on the combination of sildenafil and bosentan.
Currently the COMPASS-2 study is ongoing and to investigate the effect on morbidity and mortality of a combination of bosentan with sildenafil compared to sildenafil monotherapy.
Available clinical data
COMPASS-1 demonstrated that adding sildenafil to patients on long-term bosentan therapy produced significant hemodynamic improvements, including a significant reduction in mean pulmonary vascular resistance (PVR) observed 60 minutes after administration of a single dose of sildenafil 25 mg (-15.2% [95% CI: –20.8 to –9.6]; p < 0.0001), and a decrease in the
mean total pulmonary resistance (-13.3% [95% CI: –17.0 to –9.6]; p < 0.0001).
Milestones
2007 – COMPASS-1 study results presented at ESC2006 – COMPASS program initiated Key scientific literatureGruenig E. et al. Acute administration of sildenafil in patients with pulmonary arterial hypertension (PAH) treated with bosentan produced a
significant hemodynamic response: results of the COMPASS-1 study. European Society of Cardiology (ESC) Congress 2007 Abstract 1012