FIGURE 2.

Effects of oxycodone (Oxy) alone (a) versus combined effects of oxycodone with diazepam (b), paroxetine (c), quetiapine (d), ramelteon (e), and trazodone (f) on change from baseline arterial partial pressure of carbon dioxide (pCO₂). Shown are the univariate (a) and multivariate (b–f) linear regression results using data from the animal experiments with oxycodone alone, the sedative psychotropic drug (SPD) alone, and the SPD combined with oxycodone. The univariate linear regression for oxycodone (dark gray with 95% confidence interval [light gray]) is shown to display model‐predicted effects on change from baseline arterial pCO₂ from oxycodone alone. Multivariate linear regression models were developed for each combination of oxycodone and SPD. The resulting oxycodone relationship from the multivariate linear regression is shown on each plot for comparison with the effects from oxycodone combined with the SPD. Shown in blue are the mean change from baseline arterial pCO₂ with 95% confidence for the SPD and oxycodone combination arms (amount administered is labeled on each figure). Each point is represented on the x‐axis based on the geometric maximum concentration of all rats at that dose and/or combination. If the combination treatment is less than or overlaps with the mean effect of oxycodone alone (dark gray), this would suggest oxycodone alone could explain the observed effects on change from baseline arterial pCO₂. Likewise, if the combination effect is greater, this would suggest the drug combination is having an additional effect, which could be due to the SPD alone or synergy