List of Figures 2.1 S-ketamine PK - Plasma concentrations . . . . . . . . . . . . . . 22 2.2 S-ketaminePK-FinalPKmodel. . . . . . . . . . . . . . . . . . 26 2.3 S-ketamine PK - Goodness of Fit (GOF) plots . . . . . . . . . . 30 2.4 S-ketaminePK-Simulations . . . . . . . . . . . . . . . . . . . . 31 2.5 S-ketaminePK-SimulationsHNK . . . . . . . . . . . . . . . . . 35 3.1 S-ketamine PD - Pharmacokinetic data . . . . . . . . . . . . . . 49 3.2 S-ketamine PD - Antinociceptive data . . . . . . . . . . . . . . . 49 3.3 S-ketamine PD - Goodness-of-Fit plots . . . . . . . . . . . . . . . 52 3.4 S-ketaminePD-Drughighdata . . . . . . . . . . . . . . . . . . 53 3.5 S-ketamine PD - Visual Predictive Checks . . . . . . . . . . . . . 54 3.6 S-ketamine PD - Steady-state concentration-effect relationships . 55 4.1 Oliceridine respiratory effects - ˙VE55 for four treatment arms . . 74 4.2 Oliceridine respiratory effects - Mean pharmacokinetic data . . . 76 4.3 Oliceridine respiratory effects - Goodness-of-Fit PK data . . . . . 77 4.4 Oliceridine respiratory effects - Population PK model outcome . 78 4.5 Oliceridine respiratory effects - Population PD model outcome . 81 4.6 Oliceridine respiratory effects - Goodness-of-Fit PD data . . . . . 82 4.7 Oliceridine respiratory effects - Simulation multiple dosing . . . . 85 4.8 Oliceridine respiratory effects - Queried adverse events . . . . . . 87 5.1 CBHypoxia-Strobediagram. . . . . . . . . . . . . . . . . . . . 105 5.2 CBHypoxia-HVR..........................108 5.3 CBHypoxia-Dejour.........................109 5.4 CBHypoxia-Hemodynamics . . . . . . . . . . . . . . . . . . . . 111
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