Effect of Food, Antacid, and Age on the Pharmacokinetics of the Oral Thrombin Receptor Antagonist Vorapaxar (SCH 530348) in Healthy Volunteers

This randomized, open-label, parallel group study examined the effects of food, antacid, and age on the pharmacokinetics of vorapaxar. In total, 101 subjects were enrolled including 83 young adults (18-45 years) and 18 elderly subjects (>65 years). Subjects received single-dose vorapaxar 40 mg after a 10-hour fast (young and elderly) or with extra-strength antacid, food, or 1 or 2 hours after food (young only). Vorapaxar 40 mg was rapidly absorbed after a fast (median T-max: 1 hour). Administration with food or 1 or 2 hours post-meal modestly increased vorapaxar mean area under the curve (AUC) and C-max and prolonged median T-max by 1 hour. Concomitant food modestly increased vorapaxar AUC from time zero to infinity [AUC(I)] and Cmax 43% and 31%, respectively. Antacid modestly decreased vorapaxar AUC(I) by 15% and C-max by 38%, and increased median T-max by 1 hour. Vorapaxar AUC(I) and C-max were 41% and 29% higher, respectively, in elderly versus young subjects. Concomitant food and older age were associated with modest increases, and antacid was associated with a small decrease in vorapaxar exposure, which are not expected to affect the drug's safety or efficacy.