Pulmonary arterial hypertension (PAH) is a rare but life-threatening disease that progresses rapidly and is currently without a cure. Pharmacological treatments aim to slow down disease progression and to reduce symptoms by targeting the prostacyclin, the endothelin or the nitric oxide pathway. Drugs targeting the prostacyclin pathway have been shown to be favourable for PAH patients by causing vasodilatative, anti-proliferative as well as anti-inflammatory effects, but tend to be underused, partially due to adverse effects and difficulties associated with their intravenous administration. Treprostinil, a stable prostacyclin analogue, was FDA-approved in 2002 to improve exercise capacity in PAH patients and is available in intravenous, subcutaneous, inhaled and oral form. The four different possible ways of administration, a long half-life and its stability at room temperature give treprostinil an advantage over epoprostenol, iloprost and selexipag, the three other FDA-approved drugs targeting the prostacyclin pathway. In clinical trials, treprostinil improved exercise capacity, quality of life (QOL), functional class and clinical status. While the different forms of treprostinil lead to specific complications, its general adverse effects are dizziness, nausea, pain in the jaw and extremities, diarrhoea, flushing and headache. This MiniReview will assess the benefits and drawbacks of treprostinil in the treatment of PAH by examining its specific mechanism of action and pharmacological properties, such as pharmacokinetics, pharmacodynamics, adverse effects and interactions. In addition, we will analyse and discuss results from different clinical trials, comparing treprostinil's four different forms to each other as well as to other drugs targeting the prostacyclin pathway.
Keywords: clinical trials; prostacyclin analogue; pulmonary arterial hypertension; treprostinil.
© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).