4 Oliceridine respiratory effects Table 4.1: Pharmacokinetic parameter estimates Between-subject variability Inter-occasion variability Oliceridine Parameter ±SEE ω2 ±SEE ν2 ±SEE V1 (L/70 kg) 1.1 ±0.1 0.07 ±0.03 V2 (L/70 kg) 5.6 ±0.5 V3 (L/70 kg) 45.3 ±1.8 0.01 ±0.01 CL1 (L/h at 70 kg) 33.1 ±1.5 0.02 ±0.01 0.006 ±0.003 CL2 (L/h at 70 kg) 22.8 ±2.3 0.04 ±0.02 0.02 ±0.01 CL3 (L/h at 70 kg) 27.6 ±2.0 0.05 ±0.03 D1 (min) 1 0.83 ±0.43 CL1 PM (L/h at 70 kg) 17.8 ±1.5 σ2 0.009 ±0.001 Morphine V1 (L/70 kg) 3.3 ±0.3 0.05 ±0.02 V2 (L/70 kg) 7.1 ±0.6 V3 (L/70 kg) 90.2 ±3.7 0.02 ±0.01 CL1 (L/h at 70 kg) 80.1 ±2.3 0.016 ±0.004 CL2 (L/h at 70 kg) 35.8 ±2.3 CL3 (L/h at 70 kg) 51.4 ±2.4 D1 (min) 1.0 1.1 ±0.5 σ2 0.012 ±0.001 SEE is standard error of the estimate, ω2 inter-subject variability; V1, V2 and V3 are the volumes of compartments 1, 2 and 3, respectively; CL1 is the clearance from compartment 1 with CL1 PM is CL1 of the oliceridine poor metabolizer, CL2 and CL3 the intercompartmental clearances between compartments 1 and 2 and 1 and 3, respectively; D1 is the infusion duration; and σ2 is a measure of residual variability. 79
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