Joint population pharmacokinetic modeling of venlafaxine and O-desmethyl venlafaxine in healthy volunteers and patients to evaluate the impact of morbidity and concomitant medication

Figures

• 

  FIGURE 1. Population pharmacokinetic model structure for VEN and ODV. K a, absorption rate constant, K 23, rate constant for the conversion of VEN into ODV; K 30, elimination rate constant for ODV; V/F, apparent volume of distribution for VEN; V M/F, apparent volume of distribution for ODV; FP, fraction of VEN converted into ODV before entering the blood circulation.

• 

  FIGURE 2. Individual C-t profiles of VEN (blue) and ODV (red) in study 1 (left) and study 2 (right).

• 

  FIGURE 3. Boxplot with the median and interquartile range of the clearance of VEN (left) and ODV (right) according to health status and concomitant use of amisulpride. Box with light grey represents healthy subjects, and box with dark grey represents patients.

• 

  FIGURE 4. Diagnostic plots for VEN in the final PPK model. The left upper is the plot of the population-predicted concentrations versus the observed VEN concentrations; the right upper is the plot of the individual population-predicted concentrations versus the observed VEN concentrations; the left lower represents the conditional weighted residual error versus the population-predicted VEN concentrations; the right lower represents the conditional weighted residual error versus the time after last dose.

• 

  FIGURE 5. Diagnostic plots for ODV in the final PPK model. The left upper is the plot of the population-predicted concentrations versus the observed ODV concentrations; the right upper is the plot of the individual population-predicted concentrations versus the observed ODV concentrations; the left lower represents the conditional weighted residual error versus the population-predicted ODV concentrations; the right lower represents the conditional weighted residual error versus the time after last dose.

• 

  FIGURE 6. Results of the NPDE analysis for VEN. The left upper plot is a QQ-plot for NPDE; the right upper plot is a histogram of the NPDE; the left lower and right lower plots represent the NPDE versus time and the NPDE versus the predicted concentrations of VEN, respectively.

• 

  FIGURE 7. Results of the NPDE analysis for ODV. The left upper plot is a QQ-plot for NPDE; the right upper plot is a histogram of the NPDE; the left lower and right lower plots represent the NPDE versus time and the NPDE versus the predicted concentrations of ODV, respectively.