Ki (μM) valuesa of omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole for human P450 isoforms
Marker Reaction | Microsomes | R-Omeprazole | Omeprazole | Esomeprazole | Lansoprazole | Pantoprazole | Rabeprazole | Rabeprazole Thioether | Model Inhibitor | |
|---|---|---|---|---|---|---|---|---|---|---|
| CYP2C9 | Sulfaphenazole | |||||||||
| Diclofenac | HLM | 5.3 ± 0.4 | 16.4 ± 3.0 | 81.5 ± 72.7a | 20.8 ± 3.3 | 6.5 ± 1.0 | 51.0 ± 9.4 | 5.8 ± 0.6 | 0.15 ± 0.03 | |
| 4′-hydroxylation | ||||||||||
| CYP2C19 | Ticlopidine | |||||||||
| S-Mephenytoin | HLM | 5.8 ± 0.6 | 6.2 ± 0.8 | 8.6 ± 1.0 | 0.45 ± 0.07 | 69.4 ± 9.2 | 21.3 ± 2.8 | 2.4 ± 0.1 | 0.31 ± 0.05 | |
| 4′-Hydroxylation | rCYP2C19 | 1.7 ± 0.1 | 2.4 ± 0.05 | 7.9 ± 0.5 | 0.74 ± 0.09 | 15.3 ± 1.1 | 18.8 ± 1.3 | 2.8 ± 0.1 | 0.68 ± 0.04 | |
| R-Omeprazole | HLM | NA | NA | NT | 1.5 ± 0.2 | 17.4 ± 1.0 | 16.8 ± 1.9 | 3.1 ± 0.2 | 1.7 ± 0.2 | |
| 5-Hydroxylation | rCYP2C19 | NA | NA | NT | 0.91 ± 0.05 | 13.9 ± 0.9 | 17.3 ± 1.4 | 8.3 ± 0.8 | 0.86 ± 0.08 | |
| CYP2D6 | Quinidine | |||||||||
| Bufuralol | HLM | NT | IC50 > 200 | IC50 > 200 | IC50 > 200 | IC50 > 200 | IC50 > 200 | 12.4 ± 1.2 | 0.03 ± 0.004 | |
| 1′-Hydroxylation | ||||||||||
| CYP3A4 | Ketoconazole | |||||||||
| Midazolam | HLM | 44.5 ± 5.0 | 41.9 ± 5.9 | 46.6 ± 6.8 | IC50 > 200 | 21.9 ± 2.7 | 50.7 ± 6.4 | 15.0 ± 1.8 | 0.0052 ± 0.0005 | |
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NT, not tested; NA, not applicable.
↵ a All the Ki values were calculated with the competitive inhibition model except esomeprazole to CYP2C9-mediated diclofenac 4′-hydroxylation, which showed the best fit to the mixed inhibition model