4 Oliceridine respiratory effects Figure 4.7: Simulation of multiple dosing. Simulation study of the effect of multiple doses oliceridine and morphine, mimicking patient-controlled analgesia and aimed at a maximum level of respiratory depression of 65% of baseline ventilation. A. Oliceridine pharmacokinetics in normal metabolizers. B. Oliceridine pharmacokinetics in poor metabolizers. C. Ventilation in normal (blue line) and poor oliceridine metabolizers (red broken line). The grey area indicates the ventilation variability. D. Morphine pharmacokinetics.E. Ventilation following morphine. Panels A, Band D: green lines depict plasma concentration, red lines effect-site concentrations. Panels Cand E: grey areas depict the ventilation variability. 85
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