Clinical Medicine Reviews in Vascular Health

Pulmonary arterial hypertension (PAH) is a progressive disease process with a high morbidity and mortality. Until the advent of epoprostenol, a continuous prostacyclin infusion therapy, PAH was uniformly fatal but for those few who responded to calcium channel blockers. The development of PAH specific oral therapies including endothelin antagonists and phosphodiesterase-5 inhibitors provide effective alternatives to intravenous epoprostenol for mild to moderately symptomatic persons. But while effective, a significant number of patients fail oral therapy and require combination oral therapy and progression to prostacyclins. While epoprostenol improves quality of life and average life span in PAH, a short 4 minute half life places patients at high risk for rapid decompensation with even short interruptions of the infusion. Additionally, epoprostenol requires a complicated delivery system including a large pump and an indwelling central line that carries risk of infection and sudden occlusion. The second prostanoid developed was treprostinil which has the advantage of a 4 hr half life, stability at room temperature, and the ability to be continuously administered subcutaneously with a small pump. Subsequently, treprostinil was demonstrated to be safe and effective given intravenously and by inhalation. We will review the pharmacokinetics, dosing, metabolism, and side effects of treprostinil in its various forms and overall place in the treatment of PAH.