Voswinckel Robert, Enke Beate, Reichenberger Frank, Kohstall Markus, Kreckel Andree, Krick Stefanie, Gall Henning, Gessler Tobias, Schmehl Thomas, Ghofrani Hossein A, Schermuly Ralph Theo, Grimminger Friedrich, Rubin Lewis J, Seeger Werner, Olschewski Horst
Department of Internal Medicine, University Hospital Giessen, Giessen, Germany.
J Am Coll Cardiol. 2006 Oct 17;48(8):1672-81. doi: 10.1016/j.jacc.2006.06.062. Epub 2006 Sep 26.
This study sought to investigate the effects of inhaled treprostinil on pulmonary hemodynamics and gas exchange in severe pulmonary hypertension.
Inhaled iloprost therapy has a proven clinical efficacy in pulmonary arterial hypertension, but this therapy necessitates 6 to 9 inhalation sessions per day. Treprostinil has a longer plasma half-life and might provide favorable properties when applied by inhalation.
Three different studies were conducted on a total of 123 patients by means of right heart catheterization: 1) a randomized crossover-design study (44 patients), 2) a dose escalation study (31 patients), and 3) a study of reduction of inhalation time while keeping the dose fixed (48 patients). The primary end point was the change in pulmonary vascular resistance (PVR).
The mean pulmonary arterial pressure of the enrolled patients was approximately 50 mm Hg in all studies. In study 1, both treprostinil and iloprost at an inhaled dose of 7.5 mug displayed a comparable PVR decrease, with a significantly different time course (p < 0.001), treprostinil showing a more sustained effect on PVR (p < 0.0001) and fewer systemic side effects. In study 2, effects of inhalation were observed for 3 h. A near-maximal acute PVR decrease was observed at 30 mug treprostinil. In study 3, treprostinil was inhaled at increasing concentrations with a pulsed ultrasonic nebulizer, mimicking a metered dose inhaler. A dose of 15 mug treprostinil was inhaled with 18, 9, 3, 2 pulses, or 1 pulse, each mode achieving comparable, sustained pulmonary vasodilation without significant side effects.
Inhaled treprostinil exerts sustained pulmonary vasodilation with excellent tolerability at relatively low doses and may be inhaled in a few breaths.
本研究旨在探讨吸入用曲前列尼尔对重度肺动脉高压患者肺血流动力学和气体交换的影响。
吸入用伊洛前列素治疗肺动脉高压已被证实具有临床疗效，但该疗法需要每天进行6至9次吸入治疗。曲前列尼尔的血浆半衰期更长，吸入应用时可能具有有利特性。
通过右心导管检查对总共123例患者进行了三项不同的研究：1）一项随机交叉设计研究（44例患者），2）一项剂量递增研究（31例患者），以及3）一项在保持剂量固定的同时减少吸入时间的研究（48例患者）。主要终点是肺血管阻力（PVR）的变化。
在所有研究中，入选患者的平均肺动脉压约为50 mmHg。在研究1中，吸入剂量为7.5 μg的曲前列尼尔和伊洛前列素均显示出相当的PVR降低，时间过程有显著差异（p < 0.001），曲前列尼尔对PVR的作用更持久（p < 0.0001），全身副作用更少。在研究2中，观察到吸入作用持续3小时。在曲前列尼尔剂量为30 μg时观察到近乎最大的急性PVR降低。在研究3中，使用脉冲超声雾化器以递增浓度吸入曲前列尼尔，模拟定量吸入器。分别以18、9、3、2次脉冲或1次脉冲吸入15 μg曲前列尼尔，每种模式均实现了相当的、持续的肺血管舒张，且无明显副作用。
吸入用曲前列尼尔在相对低剂量下可产生持续的肺血管舒张，耐受性良好，且可在几次呼吸内完成吸入。
