P450 inhibition profile of E2101 in reconstituted reaction system containing HLM
| E2101 | Metabolic Rate (Mean ± S.D.)2-a2-b | |||||
|---|---|---|---|---|---|---|
| CYP1A2 | CYP2C9 | CYP2C19 | CYP2D6 | CYP2E1 | CYP3A4 | |
| μM | pmol/min/mg protein | |||||
| 0 | 4.9 ± 0.7 | 0.81 ± 0.01 | 49 ± 5 | 22 ± 0.9 | 193 ± 45 | 9.4 ± 4.3 |
| 10 | 4.3 ± 0.1 | 0.86 ± 0.00 | 44 ± 3 | 7.4 ± 2.52-160 | 142 ± 25 | 9.7 ± 1.7 |
| 50 | 4.4 ± 0.4 | 0.91 ± 0.05 | 33 ± 42-150 | 4.2 ± 0.42-160 | 185 ± 27 | 12.5 ± 1.1 |
↵2-150 Significant difference from the controls (0.01 < p < 0.05).
↵2-160 Highly significant difference from the controls (p < 0.01).
↵2-a Determined by the P450 form-specific activities including CYP1A2-mediatedR-warfarin 6-hydroxylation, CYP2C9-mediatedS-warfarin 7-hydroxylation, CYP2C19-mediatedS-mephenytoin 4′-hydroxylation, CYP2D6-mediated bufuralol 1′-hydroxylation, CYP2E1-mediated chlorozoxazone 6-hydroxylation, and CYP3A4-mediated R-warfarin 10-hydroxylation.
↵2-b N = 4.