FIGURE 4.

Model application: simulated plasma concentrations of olanzapine (a) and samidorphan (b) after once‐daily doses of OLZ/SAM 10 mg/10 mg for 14 days. The lines represent the mean data for simulated populations (n = 100) of subjects with normal hepatic function (black) and subjects with mild hepatic impairment (green), moderate hepatic impairment (blue) and severe hepatic impairment (red). Simulations assume reduced plasma protein binding in individuals with hepatic impairment. For olanzapine, the mean f_u values were 0.07, 0.08, 0.10, and 0.13 for subjects with normal hepatic function and for those with mild, moderate and severe hepatic impairment, respectively; for samidorphan, the mean f_u values were 0.69, 0.71, 0.76, and 0.81 for subjects with normal hepatic function and for those with mild, moderate and severe hepatic impairment, respectively. f_u, fraction unbound in plasma; OLZ/SAM, combination of olanzapine and samidorphan