Favorable Effects of Inhaled Treprostinil in Severe Pulmonary Hypertension

Abstract

Inhaled treprostinil exerts sustained pulmonary vasodilation with excellent tolerability at relatively low doses and may be inhaled in a few breaths.

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

“…In preceding studies we found that quite high doses of inhaled treprostinil could be safely deposited in the lung in as little as a single breath [8]. This suggested for the first time the possibility to deliver a potent vasodilator for pulmonary hypertension treatment with a metered dose inhaler.…”

“…It was an unanticipated finding that treprostinil, besides the positive consequences of a longer half life for inhalation therapy, was tolerated at single doses up to 60µg without relevant side effects. The inhalation of an effective treprostinil dose in one single breath was achieved with highly concentrated treprostinil sodium solution of 2000µg/ml without side effects [8]. We believe that the absence of systemic side effects despite rapid application of treprostinil in high doses is…”

“…In this respect it has been shown recently in macrophages that treprostinil, in opposite to PGI2 and iloprost, does not only activate the IP receptor but also the EP2 receptor [15]. Another sign for partial pulmonary vascular selectivity of treprostinil is that about two-fold dose of inhaled treprostinil achieves the same acute vasodilation as compared to inhaled iloprost [8] The aerodynamic aerosol diameter of MDI treprostinil of 4-5µm is certainly at the upper limit for alveolar deposition, so reduction of aerodynamic aerosol diameter might improve MDI-TRE deposition.…”

“…Data from this cohort has been published before [8] but we felt it would be meaningful to present a direct comparison (figure 5). The comparison (which is not an intra-individual comparison) showed quite similar responses in terms of PVR reduction for all respective dose groups.…”

Treatment options for paediatric pulmonary arterial hypertension

“…or s.c. administration [34] or inhalation [35]. Several studies that included both older children and adults demonstrated or suggested efficacy of treprostinil i.v.…”