Effect of food, an antacid, and the H2 antagonist ranitidine on the absorption of BAY 59-7939 (Rivaroxaban), an oral, direct factor Xa inhibitor, in healthy subjects

To investigate the influence of food and administration of an antacid (aluminum-magnesium hydroxide) or ranitidine on the absorption of BAY 59-7939 (rivaroxaban), 4 randomized Studies were performed in healthy male subjects. In 2 food interaction studies, subjects received BAY 59-7939, either as two 5-mg tablets (fasted and fed), four 5-mg tablets (fasted), or one 20-mg tablet (fasted and fed). In 2 drug intern action studies, BAY 59-7939 (six 5-mg tablets) was given alone or with ranitidine (150 mg twice doily, preceded by a 3-day pretreatment phase) or antacid (10 mL). Plasma samples were obtained to assess pharmacokinetic and pharmacodynamic parameters of BAY 59-7939. In the presence of food, time to maximum concentration (t(max)) was delayed by 1.25 hours; maximum concentration (C-max)and area under the curve (AUC) were increased, with reduced interindividual variability at higher doses of BAY 59-7939. Compared with baseline, BAY 59-7939 resulted in G relative increase in maximum prothrombin time (PT) prolongation of 44 % (10 mg) and 53 % (20 mg) in the fasted state, compared with 53% and 83% after food. Time to maximum PT prolongation was delayed by 0.5 to 1.5 hours after food, with no relevant influence of food type. No significant diffefference in C-max and AUC was observed with coadministration of BAY 59-7939 and ranitidine or antacid.