Effects of food on the pharmacokinetics of edoxaban, an oral direct factor Xa inhibitor, in healthy volunteers.
The primary objective of this study was to assess the effect of a standard high-fat meal on the single-dose (60 mg) pharmacokinetics (PK) of edoxaban in healthy Japanese and Caucasian male volunteers matched by body mass index. This was an open-label, randomized, 2-period crossover study. All 32 enrolled volunteers completed the study per protocol. Both serial blood and urine samples were collected, and edoxaban concentrations were analyzed by a validated liquid chromatography/tandem mass spectrometry method. Activated partial thromboplastin and prothrombin times were obtained as measures of pharmacodynamic effect. The point estimates of the geometric mean ratios (fed/fasted) for AUC(0-t), AUC(0-∞), and C(max) demonstrated modest increases ranging from 6% to 22% across PK parameters for both race cohorts. The disposition was similar in both Japanese and Caucasian matched volunteers with slightly higher AUC values (ranging from 7%-9%) in Caucasians. There were no serious adverse events during the study. All drug-related adverse events were mild and self-limited, and none were bleeding related. Both Japanese and Caucasian volunteers demonstrated a modest but clinically insignificant food effect. It was concluded that edoxaban can be administered without regard to food.
Mendell
Jeanne
J
MPH, Daiichi Sankyo Pharma Development, 399 Thornall St, Edison, NJ 08837, USA. jmendell@dsi.com
Tachibana
Masaya
M
Shi
Minggao
M
Kunitada
Satoshi
S
D000284:Administration, Oral; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D044466:Asian People; D001777:Blood Coagulation / Q000187:drug effects*; D015992:Body Mass Index; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004041:Dietary Fats; D065427:Factor Xa Inhibitors; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D053719:Tandem Mass Spectrometry; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D044465:White People; D055815:Young Adult
D000925:Anticoagulants; D004041:Dietary Fats; D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; C552171:edoxaban