Population pharmacokinetic modeling indicated that 15 mg once daily rivaroxaban in Japanese patients with atrial fibrillation yields exposures comparable to 20 mg once daily in Caucasian patients.
Does rivaroxaban 15 mg once daily in Japanese patients with AF yield comparable pharmacokinetic exposures to 20 mg once daily in Caucasian patients?
Pharmacokinetic modeling supports a reduced dose of rivaroxaban 15 mg once daily for stroke prevention in Japanese patients with atrial fibrillation.
The global ROCKET AF phase III trial evaluated rivaroxaban 20 mg once daily (o.d.) for stroke prevention in atrial fibrillation (AF). Based on rivaroxaban pharmacokinetics in Japanese subjects and lower anticoagulation preferences in Japan, particularly in elderly patients, the optimal dose regimen for Japanese AF patients was considered. The aim of this analysis was dose selection for Japanese patients from a pharmacokinetic aspect by comparison of simulated exposure in Japanese patients with those in Caucasian patients. As a result of population pharmacokinetics-pharmacodynamics analyses, a one-compartment pharmacokinetic model with first-order absorption and direct link pharmacokinetic-pharmacodynamic models optimally described the plasma concentration and pharmacodynamic models (Factor Xa activity, prothrombin time, activated partial thromboplastin time, and HepTest), which were also consistent with previous works. Steady-state simulations indicated 15 mg rivaroxaban o.d. doses in Japanese patients with AF would yield exposures comparable to the 20 mg o.d. dose in Caucasian patients with AF. In conclusion, in the context of the lower anticoagulation targets in Japanese practice, the population pharmacokinetic and pharmacodynamic modeling supports 15 mg o.d. as the principal rivaroxaban dose in J-ROCKET AF.
Tanigawa et al. (Thu,) conducted a other in Non-valvular Atrial Fibrillation. Rivaroxaban vs. Rivaroxaban 20 mg once daily in Caucasian patients was evaluated on Simulated exposure and pharmacodynamics (Factor Xa activity, prothrombin time, activated partial thromboplastin time, and HepTest). Population pharmacokinetic modeling indicated that 15 mg once daily rivaroxaban in Japanese patients with atrial fibrillation yields exposures comparable to 20 mg once daily in Caucasian patients.