Evaluation of various PPIs as inhibitors of P450s in HLM
Data represent mean ± S.D. of four different experiments performed on different days. Data in parentheses represent percentage of inhibition at the highest concentration tested (40 μM); when not reported, the percentage of inhibition was less than 10%.
| PPI | IC50 (μM) for Each P450 Form | |||||
|---|---|---|---|---|---|---|
| CYP1A2 | CYP2B6 | CYP2C8 | CYP2C9 | CYP2D6 | CYP3A4 | |
| Omeprazole | ||||||
| IC50 | >40 (48 ± 2) | >40 | >40 (27 ± 5) | >40 | >40 (27 ± 4) | >40 |
| IC50(t) | 20.6 ± 4.2 | >40 | >40 (38 ± 4) | >40 | >40 (40 ± 4) | >40 |
| Esomeprazole | ||||||
| IC50 | >40 (14 ± 7) | >40 | 31.0 ± 9.0 | >40 | >40 (45 ± 7) | >40 |
| IC50(t) | >40 (22 ± 6) | >40 (15 ± 4) | 31.9 ± 9.1 | >40 (19 ± 5) | 20.9 ± 4.8 | >40 (19 ± 5) |
| Lansoprazole | ||||||
| IC50 | 8.1 ± 2.0 | >40 | >40 | >40 (16 ± 2) | >40 | >40 (16 ± 2) |
| IC50(t) | 18.5 ± 1.9 | >40 (13 ± 7) | >40 (26 ± 14) | >40 (24 ± 6) | >40 (11 ± 6) | >40 (24 ± 6) |
| Dexlansoprazole | ||||||
| IC50 | 7.1 ± 1.4 | >40 | >40 (17 ± 6) | >40 (19 ± 5) | >40 | >40 (19 ± 5) |
| IC50(t) | 20.0 ± 0.8 | >40 (14 ± 5) | >40 (28 ± 9) | >40 (31 ± 4) | >40 | >40 (31 ± 4) |
| Pantoprazole | ||||||
| IC50 | >40 (37 ± 2) | >40 | >40 | >40 | >40 | >40 |
| IC50(t) | 31.8 ± 2.1 | >40 | >40 (12 ± 10) | >40 | >40 | >40 |
| Rabeprazole | ||||||
| IC50 | >40 | >40 | >40 (27 ± 3) | >40 | >40 (32 ± 4) | >40 |
| IC50(t) | 18.1 ± 4.8 | >40 (48 ± 4) | 13.9 ± 2.0 | >40 (27 ± 7) | 28.5 ± 1.1 | >40 (27 ± 7) |
IC50, concentration of inhibitor required to decrease activity by 50% (not corrected for fu,inc); IC50(t), concentration of inhibitor required to decrease activity by 50% after a preincubation time (t). In this instance, t = 30 min.