Simulated distributions of the individual clearance and central distribution volume parameters of selected literature PK models and the final redeveloped model describing (S)-ketamine (a and b) and (S)-norketamine (c and d) [18, 26, 27, 30, 31]. Individual parameter values were simulated 1000 times as Pi = TVP*exp(etaIIV + etaBOV), in which eta represents the IIV or BOV when reported and is normally distributed with mean 0 and variance ω2, and TVP represents the parameter value of a typical individual, being indicated with a vertical line below the corresponding distribution. Sigtermans et al. included sex as covariate on CL but not on Vd, which is why the (S)-ketamine Vd distributions of Sigtermans (males) and Sigtermans (females) overlap. The population parameters of the final redeveloped model describing (S)-ketamine were fixed to the values reported by Fanta et al.