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The Absence of a Clinically Significant Effect of Food on the Single Dose Pharmacokinetics of Vorapaxar, a PAR‐1 Antagonist, in Healthy Adult Subjects
Author(s) -
Behm Martin O.,
Kosoglou Teddy,
Miltenburg André M.M.,
Li Jing,
Statkevich Paul,
JohnsonLevonas Amy O.,
Martinho Monika,
Fackler Paul
Publication year - 2013
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.38
Subject(s) - medicine , crossover study , pharmacokinetics , geometric mean , concomitant , confidence interval , area under the curve , antagonist , anesthesia , placebo , pharmacology , statistics , alternative medicine , mathematics , pathology , receptor
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 AUC 0–72 hr and C max were analyzed by ANOVA. If 90% confidence intervals (CI) for the geometric mean ratios (GMRs; fed/fasted) of AUC 0–72 hr and C max were within the 50–200% range, then food was deemed not to have a clinically important effect. The LS geometric mean (90% CI) AUC 0–72 hr and C max 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 AUC 0–72 hr and C max 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 C max and 45‐min delay in T max ) 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.