title: Population Pharmacokinetics of Edoxaban in Japanese Atrial Fibrillation Patients With Severe Renal Impairment.
abstract: This is a population pharmacokinetic (PopPK) analysis to predict PK of edoxaban, a direct-acting oral anticoagulant, in nonvalvular atrial fibrillation (NVAF) patients with severe renal impairment (SRI; creatinine clearance [CLcr] <30 mL/min). Data from a phase 3 study recently conducted in Japanese NVAF patients (n = 90), including patients with SRI, were used to update the ENGAGE PopPK model that had been developed based on pooled data from the phase 3 ENGAGE AF-TIMI 48 study and 13 phase 1 PK studies, which included few patients with SRI. The final model indicated that the ENGAGE PopPK model was applicable to Japanese patients in that the model-simulated and study-observed concentration-time profiles were in agreement. Estimated model parameters after the addition of Japanese SRI data were consistent with those derived from the original ENGAGE PopPK data set. The model-predicted exposure in NVAF patients with SRI who received edoxaban at a 15-mg, once-daily dose was similar to that in patients with normal renal function or with mild renal impairment receiving a 30-mg dose. This suggests that efficacy and safety data from the ENGAGE AF study can be used to support dose setting for NVAF patients with SRI.
authors.affiliation: Daiichi Sankyo Co, Ltd, Nihonbashi-honcho, Chuo-ku, Tokyo, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Daiichi Sankyo Co, Ltd, Nihonbashi-honcho, Chuo-ku, Tokyo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: Daiichi Sankyo Co, Ltd, Nihonbashi-honcho, Chuo-ku, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Daiichi Sankyo Co, Ltd, Nihonbashi-honcho, Chuo-ku, Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kumakura
authors.affiliation: Daiichi Sankyo Co, Ltd, Nihonbashi-honcho, Chuo-ku, Tokyo, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yoshihara
mesh_terms: D000284:Administration, Oral; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000097:blood*; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; D003404:Creatinine; C552171:edoxaban
keywords: atrial fibrillation; edoxaban; population pharmacokinetics; severe renal impairment