贝前用于肺动脉高压流0525.ppt

Dai sukelkeda等对6名中重度肺动脉高压患者口服贝前列素和口服贝前列素及西地那非观察用药后即刻血流动力学变化。 血流动力学指标表明与单独使用贝前列素组相比，联合治疗组平均肺动脉压、肺血管阻力显著降低， 并且联合治疗时这些参数的降低较单独使用贝前列素持续的时间更长。 Addition of Oral Sildenafil to Beraprost Is a Safe and Effective Therapeutic Option for Patients with Pulmonary Hypertension Abstract: Although sildenafil, an oral phosphodiesterase type-5 inhibitor,may offer benefits in the pharmacological management of pulmonary hypertension (PH), safety and effectiveness have not been studied during coadministration with beraprost, an oral prostacyclin analogue. To address this issue, we administered oral beraprost (40 mg) on day 1 and beraprost (40 mg) plus sildenafil (25 mg) on days 2 to 6 patients with moderate to severe PH. Although sildenafil plus beraprost produced transient flushing in 2 of 6 patients, systemic hemodynamics and arterial and venous gas analyses were similar in comparisons between the 2 treatment groups. In contrast, sildenafil plus beraprost therapy resulted in a 2.2-fold greater reduction in mean pulmonary arterial pressure and a 1.6-fold greater reduction in pulmonary vascular resistance compared with beraprost alone, and reductions in these parameters persisted longer with combination therapy than with beraprost alone. Addition of oral sildenafil to beraprost appears to represent a safe and effective therapeutic option,at least in the acute phase, for patients with pulmonary hypertension * * * 凡瑞克?适用于治疗WHO功能分级为Ⅱ级或Ⅲ级的第一大类肺动脉高压患者。包括特发性、遗传性、基因突变性、药物和毒物诱导、HIV感染等引起的PAH。 * * 安立生坦是一种ETA选择性拮抗剂。通过ET-1阻断ETA活化，从而减少参与PAH发病的血管收缩和潜在的平滑肌细胞增殖。增加肺动脉血流量。 安立生坦对于ETA而非ETB的选择性，保留了ETB介导的血管扩张剂一氧化氮和前列环素的生成 。 研究内皮素受体与人心肌细胞膜结合的离体实验显示，安立生坦对ETA的配体结合亲和力较高。此外，安立生坦对ETA的选择性是ETB的4000倍。 * * * 多项II期、III期临床研究的主要评估终点是：运动耐量较基线值的变化，以6分钟步行距离(6MWD)作为评估指标。用于评估疾病的严重程度和治疗有效率。AMB-105和AMB-106：药物相互作用—探讨了安立生坦与西地那非和华法令之间存在药代动力学相互作用的可能性 AMB-220：剂量探索性研究 —II期多中心双盲剂量探索性研究，旨在探讨4种剂量安立生坦（1、2.5、5或10mg）治疗12周对于PAH患者的疗效和耐受性 AMB-222：PAH肝功能安全性的研究—多中心开放性单组研究，36例患者接受安立生坦2.5mg每日一次连续4周，然后接受5mg每日一次连续20周，然后再接受2.5、5或10mg每日一次直到试验结