The Absence of a Clinically Significant Effect of Food on the Single Dose Pharmacokinetics of Vorapaxar, a PAR-1 Antagonist, in Healthy Adult Subjects.
In this open-label, randomized, 2-period crossover study, 16 healthy subjects received a single oral 2.5-mg dose of vorapaxar in the fed (i.e., standardized high-fat breakfast) and fasted (i.e., an overnight fast) state with a 6-week washout. Plasma samples for vorapaxar assay were obtained pre-dose and up to 72 hours post-dose. Least squares (LS) geometric mean AUC0-72 hr and Cmax were analyzed by ANOVA. If 90% confidence intervals (CI) for the geometric mean ratios (GMRs; fed/fasted) of AUC0-72 hr and Cmax were within the 50-200% range, then food was deemed not to have a clinically important effect. The LS geometric mean (90% CI) AUC0-72 hr and Cmax of vorapaxar in the fasted state were 314 (284-348) ng hr/mL and 23.4 (20.7-26.4) ng/mL, respectively. The GMRs (fed/fasted) and 90% CIs for AUC0-72 hr and Cmax were 96.9 (92.2-102) and 79.1 (67.6-92.5), respectively. Vorapaxar was generally safe and well tolerated in the presence and absence of food. Concomitant food decreased the rate (i.e., 21% reduction in Cmax and 45-min delay in Tmax ) with no effect on the extent of vorapaxar absorption when administered as a single 2.5-mg dose. Thus, vorapaxar can be administered without regard to food.
Merck & Co., Inc., Whitehouse Station, NJ, USA.
Martin O
MO
Behm
Merck & Co., Inc., Whitehouse Station, NJ, USA.
Teddy
T
Kosoglou
Merck & Co., Inc., Whitehouse Station, NJ, USA.
André M M
AM
Miltenburg
Merck & Co., Inc., Whitehouse Station, NJ, USA.
Jing
J
Li
Merck & Co., Inc., Whitehouse Station, NJ, USA.
Paul
P
Statkevich
Merck & Co., Inc., Whitehouse Station, NJ, USA.
Amy O
AO
Johnson-Levonas
Merck & Co., Inc., Whitehouse Station, NJ, USA.
Monika
M
Martinho
Merck & Co., Inc., Whitehouse Station, NJ, USA.
Paul
P
Fackler
PAR-1; food; interaction; pharmacokinetics; vorapaxar