title: The potential for inhaled treprostinil in the treatment of pulmonary arterial hypertension.
abstract: Inhaled treprostinil is a safe and well-tolerated approved pharmaceutical for the treatment of pulmonary arterial hypertension. In a series of open-label studies and in the pivotal trial with 253 patients, this long-acting prostacyclin analogue demonstrated pronounced pulmonary selectivity of vasodilatory effects, improved physical capacity and excellent tolerability and safety following aerosol administration. For efficient treatment, only four daily inhalations of treprostinil are necessary compared with six to nine in iloprost aerosol therapy. This review describes in detail the development of inhaled treprostinil, starting with intravenous epoprostenol followed by inhaled iloprost and subcutaneous treprostinil, all three representing well-established and widely approved prostanoid therapies for pulmonary hypertension. In order to circumvent the drawbacks of intravenous epoprostenol, stable prostacyclin analogues with similar pharmacological properties have been investigated. In addition, alternative routes of administration have been proposed and evaluated, mainly inhaled and subcutaneous delivery. The concept of inhaled treprostinil was to combine the pulmonary selectivity of an aerosolized vasodilator with the long-acting effects of a stable prostacyclin analogue. Pulmonary arterial hypertension remains, however, a severe, life-threatening disease, in spite of the enormous progress in specific drug therapy over the last decade. Therefore, further improvement of drug therapy will be essential, with clear potential for inhaled treprostinil: a reduction of inhalation frequency and duration would markedly improve quality of life and compliance, and a longer-lasting local prostanoid effect might further enhance the efficacy of inhaled treprostinil. The advantageous pharmacological properties of treprostinil offer the opportunity to establish a convenient metered dose inhaler as a delivery system, to combine inhaled treprostinil with available or future drugs for pulmonary arterial hypertension, or to develop sustained release formulations of treprostinil suitable for inhalation based on liposomes or biodegradable nanoparticles.
authors.affiliation: Department of Internal Medicine II, Justus-Liebig-Universität Giessen, Klinikstr. 36, D-35392 Giessen, Germany. tobias.gessler@innere.med.uni-giessen.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Gessler
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmehl
mesh_terms: D000280:Administration, Inhalation; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D011464:Epoprostenol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D055118:Medication Adherence; D011788:Quality of Life
chemical_list: D000959:Antihypertensive Agents; D011464:Epoprostenol; C427248:treprostinil