TABLE 2

Evaluation of various PPIs as inhibitors of CYP2C19

Data represent mean ± S.D. of four different experiments performed on different days.

PPIIC50 (μM) for Each Substrate
(S)-Mephenytoina(S)-MephenytoinbCECbDiazepamb
Omeprazole
    IC507.4 ± 1.112.5 ± 0.41.2 ± 0.27.9 ± 1.2
    IC50(t)3.0 ± 0.2
Esomeprazole
    IC503.7 ± 0.51.3 ± 0.30.44 ± 0.094.6 ± 0.6
    IC50(t)0.76 ± 0.05
Lansoprazole
    IC500.73 ± 0.131.1 ± 0.20.41 ± 0.042.4 ± 0.3
    IC50(t)1.0 ± 0.07
Dexlansoprazole
    IC506.0 ± 1.06.2 ± 0.72.2 ± 0.513 ± 1.2
    IC50(t)5.7 ± 0.2
Pantoprazole
    IC50>40c13.4 ± 2.04.1 ± 0.67.0 ± 0.9
    IC50(t)>40c
Rabeprazole
    IC5025 ± 4.111.4 ± 1.34.2 ± 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%.