Roberts Kari E, Preston Ioana R
Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
Drug Des Devel Ther. 2009 Sep 21;3:111-8. doi: 10.2147/dddt.s3786.
Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has clearly shown that endothelin-1 (ET-1) is over-expressed in several forms of pulmonary vascular disease and plays an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) have been shown to improve exercise capacity, functional status, pulmonary hemodynamics, and delay the time to clinical worsening in several randomized placebo-controlled trials. Bosentan, the first oral ERA, was approved in 2001 and since that time it has established a strong record of safety and efficacy in PAH. More recently, two additional ERAs, ambrisentan and sitaxsentan, have been approved for use. The objective of this review is to evaluate the available evidence supporting the efficacy, pharmacology, safety and tolerability, and patient-focused perspectives for bosentan, the first approved ERA for PAH. Ongoing and forthcoming randomized trials are also highlighted including the application of bosentan in combination with other PAH therapies.
内皮素受体拮抗剂已成为治疗肺动脉高压（PAH）的一种重要方法。从实验室到临床的科学研究已明确表明，内皮素-1（ET-1）在多种形式的肺血管疾病中过度表达，并在PAH的发生和发展中起重要的致病作用。在多项随机安慰剂对照试验中，口服内皮素受体拮抗剂（ERA）已显示可改善运动能力、功能状态、肺血流动力学，并延缓临床恶化时间。首个口服ERA波生坦于2001年获批，自那时起，它在PAH治疗中建立了良好的安全性和有效性记录。最近，另外两种ERA，安立生坦和西他生坦，也已获批使用。本综述的目的是评估现有证据，以支持波生坦（首个获批用于PAH的ERA）的疗效、药理学、安全性和耐受性以及以患者为中心的观点。还重点介绍了正在进行和即将开展的随机试验，包括波生坦与其他PAH治疗方法联合应用的情况。
