Table 1.
The ability of iloperidone and lurasidone to inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 activities in vitro in human liver microsomes and human cDNA-expressed CYP enzymes (supersomes)
| CYPs isoenzymes | Inhibition of CYP-specific reactions by iloperidone and lurasidone Ki (µM) and type of inhibition | |||
|---|---|---|---|---|
| Iloperidone | Lurasidone | |||
| Liver microsomes | Supersomes | Liver microsomes | Supersomes | |
| CYP1A2 |
45 Mixed |
31 Mixed |
12.6 Mixed |
15.5 Mixed |
| CYP2C9 | – | – |
18 Mixed |
3.5 Mixed |
| CYP2C19 |
6.5 Mixed |
32 Mixed |
18 Mixed |
18.4 Mixed |
| CYP2D6 |
2.9 Competitive |
10 Competitive |
37.5 Competitive |
85 Competitive |
| CYP3A4 |
0.38 Noncompetitive |
0.3 Noncompetitive |
29.4 Competitive |
9.1 Competitive |
The presented inhibition constants (Ki) for the inhibition of particular CYP-specific reactions by iloperidone and lurasidone were obtained using a non-linear regression analysis (Program Sigma Plot 12.3; enzyme kinetics) and are shown graphically in Figs. 1, 2, 3, 4, 5 (Dixon’s plots). The mechanisms of inhibition were estimated on the basis of changes in the Km and/or Vmax values by the tested inhibitors (iloperidone and lurasidone) and are shown graphically in the inserts of Figs. 1, 2, 3, 4, 5 (Lineweaver–Burk’s plots)