Premium
Effect of Food, an Antacid, and the H 2 Antagonist Ranitidine on the Absorption of BAY 59–7939 (Rivaroxaban), an Oral, Direct Factor Xa Inhibitor, in Healthy Subjects
Author(s) -
Kubitza Dagmar,
Becka Michael,
Zuehlsdorf Michael,
Mueck Wolfgang
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006286904
Subject(s) - antacid , ranitidine , pharmacokinetics , pharmacodynamics , bay , medicine , absorption (acoustics) , chemistry , pharmacology , bioavailability , area under the curve , zoology , biology , civil engineering , physics , acoustics , engineering
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 interaction studies, BAY 59–7939 (six 5‐mg tablets) was given alone or with ranitidine (150 mg twice daily, 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 a 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 difference in C max and AUC was observed with coadministration of BAY 59–7939 and ranitidine or antacid .