Pharmacokinetic evaluation of continuous intravenous epoprostenol

Abstract

despite epoprostenol's short half-life and complicated delivery system, this treatment remains the first choice therapy for severe PAH patients.

Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects

“…The majority of the AEs was mild in intensity and observed with doses of 6 and 8 ng kg -1 min -1 for both epoprostenol ES and epoprostenol. As expected, the most commonly reported TEAEs included headache and nausea, which is consistent with the vasodilator properties of epoprostenol, the AEs described in the Flolan® [17] product monograph and previous studies in man [3,13]. Clinical laboratory evaluations, vital signs, ECGs and physical examinations did not reveal any clinically relevant effect of the infusion with epoprostenol regardless of the formulation.…”

“…To date, the PK of epoprostenol had not been fully characterized due in part to the instability of epoprostenol [23], with an in vitro half-life of 3-6 min in human blood [3]. In addition, no convenient validated bioanalytical method fulfilled the sensitivity and accuracy requirements because of the very low concentrations of epoprostenol (pg ml -1 ) reported in human plasma [24].…”

“…Among the available medications, prostacyclin (also known as prostaglandin I2, PGI2), a major metabolite of arachidonic acid produced by vascular endothelial cells, is a key natural short-acting vasoactive substance having vasodilatory, platelet inhibitory and anti-proliferative properties [3,12]. Continuous infusion with synthetic prostacyclin (epoprostenol) is generally regarded as the most effective treatment against severe cases of PAH, associated with decreased pulmonary vascular resistance, increased cardiac output (CO) and cardiac index (CIn) [13][14][15] and survival benefits [13,16].…”

Antithrombotic strategies in children receiving long-term Berlin Heart EXCOR ventricular assist device therapy

“…Owing to the short half-life of 3 to 5 minutes, it must be run as a continuous intravenous infusion and has a rapid onset of action, reaching plasma steady state within 15 minutes. 18 Our patients received relatively low doses of epoprostenol (2-4 ng/kg/min) because most were being concomitantly treated with diuretics, intravenous or oral systemic vasodilators, or sildenafil, and we did not wish to potentiate the vasodilatory effect and cause hypotension. Patients with coexisting elevation of pulmonary artery pressures were treated with higher doses.…”

Encapsulation of beraprost sodium in nanoparticles: Analysis of sustained release properties, targeting abilities and pharmacological activities in animal models of pulmonary arterial hypertension

“…Thus, PGI 2 and its analogues could be therapeutically beneficial for the treatment of PAH in affected patients [5,[10][11][12][13][14][15][16]. In fact, the intravenous administration of epoprostenol (PGI 2 ) is currently the most effective approach for the treatment of PAH, not only because it can ameliorate symptoms of severe PAH, but because it also prolongs life expectancy [16,17].…”