PPI | IC50 (μM) for Each Substrate | |||
---|---|---|---|---|
(S)-Mephenytoina | (S)-Mephenytoinb | CECb | Diazepamb | |
Omeprazole | ||||
IC50 | 7.4 ± 1.1 | 12.5 ± 0.4 | 1.2 ± 0.2 | 7.9 ± 1.2 |
IC50(t) | 3.0 ± 0.2 | |||
Esomeprazole | ||||
IC50 | 3.7 ± 0.5 | 1.3 ± 0.3 | 0.44 ± 0.09 | 4.6 ± 0.6 |
IC50(t) | 0.76 ± 0.05 | |||
Lansoprazole | ||||
IC50 | 0.73 ± 0.13 | 1.1 ± 0.2 | 0.41 ± 0.04 | 2.4 ± 0.3 |
IC50(t) | 1.0 ± 0.07 | |||
Dexlansoprazole | ||||
IC50 | 6.0 ± 1.0 | 6.2 ± 0.7 | 2.2 ± 0.5 | 13 ± 1.2 |
IC50(t) | 5.7 ± 0.2 | |||
Pantoprazole | ||||
IC50 | >40c | 13.4 ± 2.0 | 4.1 ± 0.6 | 7.0 ± 0.9 |
IC50(t) | >40c | |||
Rabeprazole | ||||
IC50 | 25 ± 4.1 | 11.4 ± 1.3 | 4.2 ± 1.3 | >40c |
IC50(t) | 21 ± 0.7 |
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.
↵a Data obtained with HLM as the enzyme source.
↵b Data obtained with rCYP2C19. IC50(t) was not determined.
↵c IC50 was greater than the highest tested concentration of PPI (40 μM); the percentage of inhibition observed at 40 μM was less than 10%.