2 S-ketamine oral thin film pharmacokinetics Table 2.4: S-ketamine OTF pharmacokinetics Parameter Estimate SEE Inter-subject variability (ω2) SEE Inter-occasion variability (ν2) SEE S-ketamine mucosal absorption from OTF F1 (bioavailability) % 26.3 1.2 0.060 0.019 D1 (duration of absorption) min 13.1 1.0 0.154 0.033 Absorption rate constant; KA1 (min-1) 0.04 0.002 0.062 0.014 Outlier (id = 4, occ = 2) for KA1 (min-1) 0.012 0.0004 Volume of S-ketamine compartment 1; VK1 (L @ 70 kg) 11.6 0.9 0.057 0.019 Volume of S-ketamine compartment 2; VK2 (L @ 70 kg) 39.0 2.9 Volume of S-ketamine compartment 3; VK3 (L @ 70 kg) 174 11 Clearance from VK1 towards metabolism compartment MK; CLK1 (L/min @ 70 kg) 1.48 0.06 0.029 0.012 Clearance from VK1 to VK2; CLK2 (L/min @ 70 kg) 2.43 0.24 Clearance from VK1 to VK3; CLK3 (L/min @ 70 kg) 1.21 0.08 0.026 0.014 sRelative (relative within subject variability) 0.012 0.0004 S-ketamine absorption from the gastrointestinal tract F2 (bioavailability) % 116 6 0.057 0.031 D2 (duration of infusion) min 29.9 3.5 0.611 0.120 Absorption rate constant; KA2 (min-1) 0.049 0.007 0.376 0.150 Mean transit time GUT (min) 10.7 1.7 0.937 0.312 27
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