Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension

被引:33
作者
Voswinckel, Robert [1 ]
Reichenberger, Frank [1 ]
Gall, Henning [1 ]
Schmehl, Thomas [1 ]
Gessler, Tobias [1 ]
Schermuly, Ralph Theo [2 ]
Grimminger, Friedrich [1 ]
Rubin, Lewis J. [3 ]
Seeger, Werner [1 ]
Ghofrani, Hossein A. [1 ]
Olschewski, Horst [1 ,4 ]
机构
[1] Univ Giessen Lung Ctr, Univ Hosp Giessen, Dept Internal Med, D-35392 Giessen, Germany
[2] Max Planck Inst Heart & Lung Res, Bad Nauheim, Germany
[3] Univ Calif San Diego, Sch Med, Div Pulm & Crit Care Med, La Jolla, CA 92093 USA
[4] Med Univ Graz, Div Pulm, Graz, Austria
关键词
Prostacyclin; Pulmonary hypertension; Pulmonary heart disease; Treprostinil sodium; Metered dose inhaler; Aerosol; ARTERIAL-HYPERTENSION; PROSTACYCLIN ANALOG; CONTROLLED TRIAL; ILOPROST; THERAPY; SILDENAFIL; EFFICACY; INFUSION; SAFETY;
D O I
10.1016/j.pupt.2008.11.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: The stable prostanoid analogue treprostinil is approved as continuous infusion for treatment of pulmonary arterial hypertension. Unique drug characteristics may render this prostanoid feasible for inhalation therapy with a metered dose inhaler. Methods and results: Randomised open label investigation of acute haemodynamic effects, safety and tolerability of inhaled treprostinil delivered in seconds by a metered dose inhaler (MDI-TRE). Inhaled nitric oxide (NO) and MDI-TRE were applied once during right heart catheter investigation to 39 consecutive patients with pre-capillary pulmonary hypertension. Doses of 30 mu g, 45 mu g and 60 mu g MDI-TRE were investigated in separate groups of patients. Haemodynamics and blood gases were measured for 2 h following treprostinil application. Acute haemodynamic responses to NO and MDI-TRE were comparable. MDI-TRE significantly improved haemodynamics compared to placebo inhalation. MDI-TRE induced effects were comparable to a historical control group that inhaled treprostinil from an ultrasonic nebuliser. The 120 min area under the curve for PVR changes due to placebo, 30 mu g, 45 mu g or 60 mu g MDI-TRE was 1114 +/- 998, -870 +/- 940, -2450 +/- 2070 and -2000 +/- 900 min*%. Reduction of systemic vascular resistance and pressure were not clinically relevant. No significant side effects were observed. No impact on ventilation/perfusion matching by treprostinil was demonstrated in 5 patients with pre-existing gas exchange limitations by use of the multiple inert gas elimination technique. Conclusions: The application of inhaled treprostinil with a metered dose inhaler is feasible and well tolerated. It induced a sustained pulmonary selective vasodilatation. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:50 / 56
页数:7
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