Effect of sodium valproate on aripiprazole pharmacokinetics and initial dosage optimization in bipolar disorder

Figure 1 Visualized evaluation. A: Observations vs individual predictions; B: Conditional weighted residuals vs individual predictions; C: Conditional weighted residuals vs time; D: Density vs weighted residuals; E: Quantiles of weighted residuals vs quantiles of normal; F: Visual predictive check. WRES: Weighted residuals.

Figure 2 Individual plots. ID: Patient ID number; DV: Measured concentration value; IPRED: Individual predictive value; PRED: Population predictive value.

Figure 3 Aripiprazole clearance rate in patients with bipolar disorder. a, patients with bipolar disorder without receiving sodium valproate sustained-release tablets. b, patients with bipolar disorder receiving sodium valproate sustained-release tablet. CL/F: Apparent oral clearance.

Figure 4 Simulated aripiprazole concentrations in patients with bipolar disorder without receiving sodium valproate sustained-release tablets. A-H: Patients with bipolar disorder without receiving sodium valproate sustained-release tablets were simulated to receive an aripiprazole dosage of (A) 0.1 mg/kg, (B) 0.2 mg/kg, (C) 0.3 mg/kg, (D) 0.4 mg/kg, (E) 0.5 mg/kg, (F) 0.6 mg/kg aripiprazole, (G) 0.7 mg/kg, and (H) 0.8 mg/kg. CI: Confidence interval.

Figure 5 Simulated aripiprazole concentrations in patients with bipolar disorder receiving sodium valproate sustained-release tablets. A-H: Patients with bipolar disorder receiving sodium valproate sustained-release tablets were simulated to receive an aripiprazole dosage of (A) 0.1 mg/kg, (B) 0.2 mg/kg, (C) 0.3 mg/kg, (D) 0.4 mg/kg, (E) 0.5 mg/kg, (F) 0.6 mg/kg aripiprazole, (G) 0.7 mg/kg, and (H) 0.8 mg/kg. CI: Confidence interval.

Figure 6 Probability within the therapeutic window range of aripiprazole in patients with bipolar disorder without receiving sodium valproate sustained-release tablets. A: Patients with bipolar disorder without receiving sodium valproate sustained-release tablets were simulated to receive an aripiprazole dosage of (A) 0.1 mg/kg, (B) 0.2 mg/kg, (C) 0.3 mg/kg, (D) 0.4 mg/kg, (E) 0.5 mg/kg, (F) 0.6 mg/kg aripiprazole, (G) 0.7 mg/kg, and (H) 0.8 mg/kg.

Figure 7 Probability within the therapeutic window range of aripiprazole in patients receiving bipolar disorder with sodium valproate sustained-release tablets. A: Patients with bipolar disorder receiving sodium valproate sustained-release tablets were simulated to receive an aripiprazole dosage of (A) 0.1 mg/kg, (B) 0.2 mg/kg, (C) 0.3 mg/kg, (D) 0.4 mg/kg, (E) 0.5 mg/kg, (F) 0.6 mg/kg aripiprazole, (G) 0.7 mg/kg, and (H) 0.8 mg/kg.