Inhibition constant (Ki, mean ± S.D., micromolar) of S-[13C7]omeprazole and R-omeprazole to each other's 5′-O-demethylation, 5- and 3-hydroxylation, and sulfoxidation in human liver microsomes, recombinant CYP2C19, and CYP3A4 All inhibitions were best described by the competitive inhibition model.
R-Omeprazole (Substrate) | S-[13C7]Omeprazole (Substrate) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Metabolic Reaction | S-[13C7]Omeprazole (Inhibitor) | R-Omeprazole (Inhibitor) | ||||||||
| HLM | rCYP2C19 | rCYP3A4 | HLM | rCYP2C19 | rCYP3A4 | |||||
| 5-Hydroxylation | 11.3 ± 0.57 | 11.6 ± 0.8 | 64.9 ± 3.5 | 42.1 ± 3.8 | 1.23 ± 0.10 | 118.6 ± 8.9 | ||||
| 5′-O-Demethylation | 27.9 ± 1.5 | 13.3 ± 0.8 | 121.9 ± 7.3 | 28.9 ± 2.2 | 1.34 ± 0.11 | 175.5 ± 14.9 | ||||
| 3-Hydroxylation | 20.3 ± 0.88 | 36.9 ± 2.0 | 38.1 ± 2.6 | 47.8 ± 3.4 | ||||||
| Sulfone formation | 15.6 ± 0.63 |
| 41.6 ± 2.3 | 91.0 ± 10.6 |
| 97.7 ± 7.9 | ||||