Fig. 1.

The influence of iloperidone and lurasidone on the activity of CYP1A2 measured as a rate of caffeine 3-N-demethylation. a Human liver microsomes (iloperidone: K_m = 293 µM, V_max = 64.7 pmol/mg protein/min; lurasidone: K_m = 407.6 µM, V_max = 57.96 pmol/mg protein/min). b Human cDNA-expressed CYP1A2 (Supersomes CYP1A2) (iloperidone: K_m = 571 µM, V_max = 3.68 pmol/mg protein/min; lurasidone: K_m = 617 µM, V_max = 1.74 pmol/mg protein/min). Each point represents the mean value of two independent analyses. V velocity of the reaction, I the concentration of the inhibitor (iloperidone or lurasidone), S the concentration of the substrate (caffeine). The K_i values and mechanisms of inhibition are shown in Table 1. Dixon’s plots (the main plots): the caffeine concentration of 200 µM (filled square), 400 µM (filled upwardtriangle) and 800 µM (filled downward triangle). Lineweaver–Burk’s plots (inserts): control—no inhibitor (no iloperidone or lurasidone) (asterisk); the inhibitor (iloperidone or lurasidone) concentration of 0.5 µM (cross mark), 1 µM (unfilled circle), 5 µM (unfilled square) and 10 µM (unfilled upward triangle)