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Population Pharmacokinetics of Edoxaban in Japanese Atrial Fibrillation Patients With Severe Renal Impairment
Author(s) -
Shimizu Takako,
Tachibana Masaya,
Kimura Tetsuya,
Kumakura Tomohiko,
Yoshihara Kazutaka
Publication year - 2016
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.329
Subject(s) - medicine , edoxaban , atrial fibrillation , renal function , pharmacokinetics , creatinine , population , intensive care medicine , warfarin , dabigatran , environmental health
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 [CL cr ] <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.