Norketamine formation from ketamine demethylation catalyzed by coexpressed wild-type CYP2B6.1, P450 oxidoreductase variants, and cytochrome b₅. Symbols are the means ± SD of triplicate determinations. Lines are predicted concentrations based on kinetic parameters obtained by nonlinear regression analysis of measured concentrations. (•) S-norketamine from S-ketamine substrate; (▴) R-norketamine from R-ketamine substrate; (○) S-norketamine from racemic RS-ketamine substrate; (△) R-norketamine from racemic RS-ketamine substrate. CYP, cytochrome P450.