Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, 1600 SW Archer Road, M452A, Gainesville, FL 32610, USA.
Respir Med. 2010 Jan;104(1):9-21. doi: 10.1016/j.rmed.2009.07.015. Epub 2009 Aug 15.
Pulmonary arterial hypertension is a chronic, progressive disease characterized by elevation of pulmonary artery pressure and pulmonary vascular resistance that ultimately results in right ventricular failure and death. Multiple mechanisms are involved in the pathogenesis of pulmonary arterial hypertension, including prostacyclin, endothelin-1, and nitric oxide pathways amongst others. The first agent to be approved for the treatment of pulmonary arterial hypertension was synthetic prostacyclin (epoprostenol), followed by prostaglandin analogs (iloprost, treprostinil, and beraprost [Japan and Korea]), which act on prostaglandin receptors. This article reviews the physiology and pathophysiology of prostanoids, summarizes key clinical studies of prostaglandin analogs for the treatment of pulmonary arterial hypertension, and discusses important pharmacokinetic and pharmacodynamic distinctions between the various prostaglandin analogs. Different prostaglandin analogs have disparate binding affinities for the various prostaglandin receptors and different G-protein-coupled receptor interactions, which may result in varying clinical efficacy and safety depending on the target tissue. Differences in formulation, route of administration, effectiveness, and safety may all play a role in deciding which prostaglandin analog to prescribe for an individual patient. Head-to-head studies will be needed to confirm differences in efficacy and safety for the various prostaglandin analogs.
肺动脉高压是一种慢性、进行性疾病，其特征为肺动脉压和肺血管阻力升高，最终导致右心衰竭和死亡。多种机制参与肺动脉高压的发病机制，包括前列环素、内皮素-1 和一氧化氮途径等。第一种被批准用于治疗肺动脉高压的药物是合成前列环素（依前列醇），随后是前列腺素类似物（伊洛前列素、曲前列尼尔和贝前列素[日本和韩国]），它们作用于前列腺素受体。本文综述了前列腺素的生理学和病理生理学，总结了前列腺素类似物治疗肺动脉高压的关键临床研究，并讨论了各种前列腺素类似物之间重要的药代动力学和药效动力学差异。不同的前列腺素类似物对各种前列腺素受体的结合亲和力不同，与 G 蛋白偶联受体的相互作用也不同，这可能导致不同的临床疗效和安全性，取决于靶组织。不同的制剂、给药途径、有效性和安全性差异都可能在决定为个体患者开哪种前列腺素类似物方面发挥作用。需要进行头对头研究来证实各种前列腺素类似物在疗效和安全性方面的差异。
