Ghosh Raktim K, Ball Somedeb, Das Avash, Bandyopadhyay Dhrubajyoti, Mondal Samhati, Saha Debjit, Gupta Anjan
Department of Cardiovascular Medicine, St. Vincent Charity Medical Center, A Teaching Hospital of Case Western Reserve University, Cleveland, OH, USA.
Department of Cardiology, Apollo Gleneagles Hospital Limited, Kolkata, India.
J Clin Pharmacol. 2017 May;57(5):547-557. doi: 10.1002/jcph.834. Epub 2016 Dec 21.
Pulmonary arterial hypertension (PAH) is a relatively rare disease that, due to its chronic nature, has always been difficult to treat effectively. Selexipag is an oral prostacyclin (PGI ) agonist that was approved by US Food and Drug Administration (US FDA) in December 2015 for the treatment of PAH. After its success in phase 1 and phase 2 clinical trials regarding the convenient oral twice-daily dosing and low side-effect profile, selexipag raised the hope of controlling the disease progression in PAH patients. In the recently completed multicentered phase 3 study (GRIPHON), selexipag has been shown to reduce death and hospitalization due to PAH significantly, an effect that was consistent across different ranges of maintenance dose. In the same study selexipag use was also associated with an increase in 6-minute walk distance (a measure of symptom severity) from baseline, but no significant improvement in all-cause mortality could be observed. The results of the ongoing phase 3 studies (TRITON and TRANSIT-1) are expected to throw some more light on the safety and efficacy of this novel molecule across various treatment scenarios. Hence, our article aims to summarize all the available information from preclinical and clinical studies published to date on the pharmacodynamics, pharmacokinetics, efficacy, safety (in general and in scenarios such as hepatic and renal function impairment), significant drug interactions (with warfarin and antiretroviral drugs), and clinical significance of oral selexipag in patients with PAH.
肺动脉高压（PAH）是一种相对罕见的疾病，由于其慢性病程，一直难以得到有效治疗。司来帕格是一种口服前列环素（PGI）激动剂，于2015年12月获美国食品药品监督管理局（US FDA）批准用于治疗PAH。在1期和2期临床试验中，司来帕格每日口服两次给药方便且副作用小，这使其有望控制PAH患者的疾病进展。在最近完成的多中心3期研究（GRIPHON）中，司来帕格已被证明可显著降低PAH导致的死亡和住院率，且在不同维持剂量范围内效果一致。在同一研究中，使用司来帕格还使6分钟步行距离（症状严重程度的一项指标）较基线有所增加，但未观察到全因死亡率有显著改善。正在进行的3期研究（TRITON和TRANSIT-1）的结果有望进一步阐明这种新型药物在各种治疗情况下的安全性和有效性。因此，我们的文章旨在总结迄今为止发表的关于司来帕格的临床前和临床研究的所有可用信息，内容涉及药效学、药代动力学、疗效、安全性（总体以及在肝肾功能损害等情况下）、显著的药物相互作用（与华法林和抗逆转录病毒药物）以及司来帕格口服给药对PAH患者的临床意义。
