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

BackgroundThe 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 resultsRandomised 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 μg, 45 μg and 60 μg 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 μg, 45 μg or 60 μg 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.ConclusionsThe application of inhaled treprostinil with a metered dose inhaler is feasible and well tolerated. It induced a sustained pulmonary selective vasodilatation.