Population Pharmacokinetics and Dose Optimization Based on Renal Function of Rivaroxaban in Thai Patients with Non-Valvular Atrial Fibrillation

Figures

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  Figure 1. Goodness-of-fits of the final population pharmacokinetic model of rivaroxaban. (A) Observed rivaroxaban concentrations vs. population predictions, (B) observed rivaroxaban concentrations vs. individually predicted concentrations, (C) conditionally weighted residual vs. time, and (D) conditionally weighted residual vs. population predictions. The open circles represent the observed rivaroxaban concentrations. The solid black lines are the line of identity or zero-line. The dashed red lines are loess smooth lines (trend lines).

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  Figure 2. The simulated 90% prediction interval from the final population pharmacokinetic model of rivaroxaban. The open circles represent the observed rivaroxaban concentrations. Solid red line represents the 50th percentile of the observations. The shaded area represents the 90% prediction interval of the simulations (n = 1000).

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  Figure 3. Simulated maximum concentration (CMAX) of rivaroxaban with different dosing regimens. The boxplots represent the predicted CMAX stratified by creatinine clearance and body weight. (A) rivaroxaban 10 mg once daily. (B) rivaroxaban 15 mg once daily. (C) rivaroxaban 20 mg once daily. The dashed lines represent the 5th and 95th percentile ranges of the typical CMAX (184–343 ng/mL) reported in patients with non-valvular atrial fibrillation receiving 20 mg of rivaroxaban [19].

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  Figure 4. Simulated minimum concentration (CMIN) of rivaroxaban with different dosing regimens. The boxplots represent the predicted CMIN stratified by creatinine clearance and body weight. (A) rivaroxaban 10 mg once daily. (B) rivaroxaban 15 mg once daily. (C) rivaroxaban 20 mg once daily. The dashed lines represent the 5th and 95th percentile ranges of the typical CMIN (12–137 ng/mL) reported in patients with non-valvular atrial fibrillation receiving 20 mg of rivaroxaban [19].

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  Figure 5. Simulated AUC0–24 of rivaroxaban with different dosing regimens. The solid black lines represent the median AUC0–24 The shaded areas represent the 90% prediction interval of the model. The dashed lines represent the 5th and 95th percentile ranges of the typical AUC0–24 (1860–5434 ng·h/mL) reported in patients with non-valvular atrial fibrillation receiving 20 mg of rivaroxaban [19].

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  Figure 6. Proportion of patients having predicted CMAX, CMIN, and AUC0–24 within the typical exposure ranges reported in patients with non-valvular atrial fibrillation [19] (1000 simulations per subgroup).