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.
MPH, Daiichi Sankyo Pharma Development, 399 Thornall St, Edison, NJ 08837, USA. jmendell@dsi.com
Jeanne
J
Mendell
Masaya
M
Tachibana
Minggao
M
Shi
Satoshi
S
Kunitada
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