Rivaroxaban population pharmacokinetic and pharmacodynamic models adequately described the data in 161 patients with non-valvular atrial fibrillation, confirming the dose selection for ROCKET AF.
Observational (n=161)
What are the population pharmacokinetic and pharmacodynamic characteristics of rivaroxaban in patients with non-valvular atrial fibrillation?
This PK/PD modeling study confirms the appropriateness of the rivaroxaban dosing regimens (20 mg and 15 mg daily based on renal function) used in the ROCKET AF trial for stroke prevention in atrial fibrillation.
Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re-estimate values of the models' parameters for the current AF population. An oral one-compartment model with first-order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post-dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal function (on prothrombin time; prothrombinase-induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF.
Girgis et al. (Wed,) conducted a observational in non-valvular atrial fibrillation (n=161). Rivaroxaban vs. Warfarin was evaluated on Pharmacokinetic and pharmacodynamic parameters. Rivaroxaban population pharmacokinetic and pharmacodynamic models adequately described the data in 161 patients with non-valvular atrial fibrillation, confirming the dose selection for ROCKET AF.