Pharmacokinetics (PK) and hemodynamics of two formulations of epoprostenol sodium for injection, epoprostenol with expanded stability (EPO-ES, Veletri®) and epoprostenol (EPO, Flolan®), were compared in an open-label, crossover, ascending-dose study in healthy males. Subjects received sequential, 2-hour (h) infusions of EPO-ES or EPO at 2, 4, 6 and 8ng/kg/min. Due to the short half-life (t1/2) of epoprostenol sodium, plasma PK were assessed via the concentration versus time profiles of two primary metabolites, 6-keto-prostacyclin F1α (kPF) and 6,15-diketo-13,14-dihydro-prostacyclin F1α (ddPF). Plasma concentration-versus-time profiles of EPO-ES and EPO with regard to kPF and ddPF were superimposable. Levels of kPF and ddPF 2h after the end of each infusion were comparable. Geometric means of the total area under the curve (AUC 0-∞ ) for kPF, were 2021 and 1972pg·h/mL (90% CI of geometric mean ratio (GMR): 97, 107), and 665 and 654pg.h/mL (90% CI of GMR: 94, 111) for ddPF following administration of EPO-ES and EPO, respectively. Similar changes in hemodynamic variables were observed during EPO-ES and EPO infusion. Average maximum increases from baseline were approximately 30% in both cardiac output and cardiac index with either formulation, and 19% and 27% in heart rate for EPO-ES and EPO, respectively. Both formulations had comparable treatment-emergent adverse event (TEAE) profiles. Headache was the most common TEAE reported. Overall, EPO-ES and EPO have the same PK, hemodynamic, safety, and tolerability profiles.