Figure 2.3: Goodness-of-fit plots for S-ketamine (A-C), S-norketamine (D-F) and S-hydroxynorketamine (G-I). A, Dand G: measured concentration versus individual predicted. B, E and H: individual weighted residuals versus time. C, F and I: Normalized discrepancy errors versus time. Simulations The results of the in-silico simulations are given in Figure 2.4 on page 31. Increasing the duration of 50 mg oral thin film application in the mouth increased peak S-ketamine concentration by a factor of 2, while reducing the duration of the film in the mouth reduced peak S-ketamine concentration accordingly (Figure 2.4A). Both S-norketamine and S-hydroxynorketamine peak concentrations changed reciprocally to the changes in S-ketamine (Figure 2.4B,C) due to changes in the first-pass effect. 30
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