| Title | Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension. | | Author(s) | Voswinckel R, Reichenberger F, Gall H, Schmehl T, Gessler T, Schermuly RT, Grimminger F, Rubin LJ, Seeger W, Ghofrani HA, Olschewski H | | Institution | University of Giessen Lung Center, Department of Internal Medicine, University Hospital Giessen, Klinikstrasse 36, 35392 Giessen, Germany. | | Source | Pulm Pharmacol Ther 2008 Nov 30. | | Abstract | 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 30mug, 45mug and 60mug MDI-TRE were investigated in separate groups of patients. Haemodynamics and blood gases were measured for 2h 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 120min area under the curve for PVR changes due to placebo, 30mug, 45mug or 60mug MDI-TRE was 1114+/-998, -870+/-940, -2450+/-2070 and -2000+/-900min*%. 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19071225 |
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