Use
Treprostinil sodium has been launched for the treatment of pulmonary hypertension.
This synthetically designed tricyclic benzindene analog of the natural potent vasodilator
prostacyclin has been developed for subcutaneous infusion. Treprostinil sodium can be
prepared in a 15 step stereoselective process. It has been suggested that treprostinil
sodium acts via the prostacyclin receptor since the agent could only increase CAMP in
human embryonic kidney cells transiently transfected with the human prostacyclin
receptor. In a conscious spontaneously hypertensive rat model, treprostinil sodium
reduced hypoxia-induced increases in pulmonary arterial pressure and pulmonary vascular
resistance in a dose-related manner. At higher doses, the test compound reduced
systemic arterial pressure and systemic vascular resistance. In patients with primary
pulmonary arterial hypertension, a one year therapy with treprostinil improved
hemodynamics parameters: a 22% improvement in cardiac output, a 24% significant
decrease in peripheral vascular resistance, a decrease in mean pulmonary arterial
pressure (55 vs. 58 mmHg at baseline) and an improvement in NYHA functional class
were observed. In addition, 6-min walk distance was significantly improved (463 vs. 399 m
at baseline). A larger study conducted in 470 patients with pulmonary arterial hypertension
has demonstrated the same type of result. In patients with severe intermittent claudication,
infusion of treprostinil was well tolerated and increased the blood flow in most of the
peripheral arteries of the lower limb. Treprostinil is eliminated in a biphasic distribution with
a terminal half-life of 2-4 h. Approximately 79% of the administrated dose is excreted in the
urine. Thus, treprostinil, in contrast to the currently available epoprostenol remains
biologically active for a longer time and is not sensitive to light and temperature. Moreover,
the subcutaneous administration avoids the epoprostenol systemic side effects due to
continuous surgically implanted intravenous infusion. Treprostinil is well tolerated by
patients and the main adverse effects currently observed are injection site reaction and
injection site pain.