RT Journal Article
SR Electronic
T1 Comparison of the pharmacokinetic, pharmacodynamic, and safety profiles of three different formulations of intravenous epoprostenol sodium
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P945
VO 40
IS Suppl 56
A1 Laurent Nicolas
A1 Marcelo Gutierrez
A1 Jasper Dingemanse
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P945.abstract
AB A change in excipient of epoprostenol sodium, an i.v. pulmonary arterial hypertension treatment, from glycine-mannitol (epoprostenol GM; Flolan®) to arginine-mannitol (epoprostenol AM; Veletri®) or to undisclosed excipients (epoprostenol XX) has led to improvements in stability of the latter two formulations.The pharmacokinetic (PK), haemodynamic, safety, and tolerability profiles of these formulations were compared in this 2-part study. 20 healthy males in Part 1 and 20 different subjects in Part 2 received epoprostenol AM and epoprostenol XX, and epoprostenol GM and epoprostenol XX, respectively, in a crossover design, in sequential 2h i.v. infusions of 2, 4, 6 and 8 ng/kg/min.PK profiles were assessed by analysing plasma concentration-time curves of the primary epoprostenol metabolites 6-keto-prostacyclin F1α (kPF) and 6,15-diketo-13,14-dihydro-prostacyclin F1α (ddPF) obtained after treatment with the different epoprostenol formulations. For Part 1, the ratio of the geometric means (90% CI) of AUC0–∞ calculated after epoprostenol AM and epoprostenol XX treatment was 0.91 (0.88–0.95) for kPF and 0.88 (0.84–0.92) for ddPF. For Part 2, the ratio of AUC0–∞ determined after epoprostenol GM and epoprostenol XX treatment was 0.97 (0.91–1.03) for kPF and 1.08 (1.02–1.14) for ddPF. Haemodynamic variables, assessed by echocardiography, showed similar increases in cardiac output, cardiac index, and heart rate for all formulations with maximum values attained after 6–8h. Almost all subjects reported ≤1 adverse event.These results suggest the 3 formulations of i.v. epoprostenol sodium have the same PK, haemodynamic, safety, and tolerability profiles.