No differences in the pharmacodynamics and pharmacokinetics of the thrombin receptor antagonist vorapaxar between healthy Japanese and Caucasian subjects

Abstract

There were no substantial differences in the safety, pharmacokinetics or pharmacodynamics of vorapaxar between Japanese and Caucasian subjects.

In vitro pharmacological characterization of vorapaxar, a novel platelet thrombin receptor antagonist

“…7. Similar observations have been made in normal human volunteers and patients dosed with vorapaxar (Kosoglou et al, 2012a(Kosoglou et al, , 2012b. As a consequence, the data suggest that achieving intermediate inhibitory levels of platelet aggregation with dose adjustments of vorapaxar are unlikely to succeed.…”

Parmodulins inhibit thrombus formation without inducing endothelial injury caused by vorapaxar

“…Importantly, endothelial injury was observed at concentrations approximating vorapaxar plasma levels achieved with dosing protocols used in TRACER or TRA-2P, as indicated by earlier pharmacokinetic studies. 37,38 The fact that PAR1 knockdown increased susceptibility of endothelial cells to vorapaxar-induced apoptosis suggests that constitutive PAR1 signaling is required for endothelial cell viability. Impaired endothelial growth and vascular formation were observed during development in PAR1 2/2 mice, 33,34 indicating that PAR1 functions in endothelial cell viability in vivo.…”

Overview of the 2014 Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee Meeting About Vorapaxar

“…The sponsor-summarized data from the vorapaxar clinical development program were extensive and included data from >41 000 patients (Table 1). 12,13,[16][17][18][19][20][21] TRACER and TRA 2 0 P-TIMI 50: A Tale of 2 Trials Vorapaxar was studied in 2 phase 3 trials, TRACER and TRA 2 0 P-TIMI 50, 12,13 that were conducted with separate and distinct patient populations, indications, inclusion and exclusion criteria, and study coordination oversight. 22 The Duke Clinical Research Institute coordinated the TRACER study; the TRA 2 0 P-TIMI 50 was coordinated by the TIMI 23 presented their summarized data and formal recommendations to the advisory committee concerning the indication for vorapaxar.…”