Table 2.
RAF normalized rates of 3-hydroxycarbamazepine (10 μM) conversion to 2,3-diOHCBZ by cDNA-expressed human P450 enzymes.
| Human Liver Microsomal Sample | RAF
|
3-OHCBZ (10 μM) conversion to 2,3-diOHCBZ
|
Clearance
|
|||||
|---|---|---|---|---|---|---|---|---|
| CYP2C19 | CYP3A4 | CYP2C19a | CYP3A4a | Total | Measured | CYP2C19 | CYP3A4 | |
| H003 | 2.6 | 33.9 | 1.2 | 6.8 | 8.0 | 5.6 | 0.12 | 0.98 |
| H006 | 2.1 | 16.7 | 1.0 | 3.3 | 4.3 | 5.7 | 0.10 | 0.48 |
| H023 | 3.6 | 19.8 | 1.7 | 3.9 | 5.6 | 4.8 | 0.16 | 0.57 |
| H024 | 2.1 | 22.8 | 1.0 | 4.5 | 5.5 | 5.1 | 0.09 | 0.66 |
| H030 | 19.1 | 48.9 | 9.0 | 9.7 | 18.7 | 16.5 | 0.86 | 1.42 |
| H042 | 0.4 | 83.3 | 0.2 | 16.6 | 16.8 | 20.3 | 0.02 | 2.42 |
| H056 | 28.6 | 29.4 | 13.5 | 5.9 | 19.4 | 14.7 | 1.29 | 0.85 |
| H064 | 1.0 | 10.0 | 0.5 | 2.0 | 2.5 | 5.9 | 0.05 | 0.29 |
| H088 | 10.1 | 27.2 | 4.8 | 5.4 | 10.2 | 9.6 | 0.46 | 0.79 |
| H089 | 11.3 | 66.7 | 5.3 | 13.3 | 14.6 | 17.1 | 0.51 | 1.93 |
| H093 | 2.3 | 9.4 | 1.1 | 1.9 | 3.0 | 4.7 | 0.10 | 0.27 |
| H095 | 1.8 | 4.2 | 0.8 | 0.9 | 1.7 | 2.7 | 0.08 | 0.12 |
| H103 | 1.3 | 15.6 | 0.6 | 3.1 | 3.7 | 7.4 | 0.06 | 0.45 |
| H112 | 22.6 | 138.9 | 10.7 | 27.6 | 38.3 | 39.6 | 1.02 | 4.03 |
a
Estimated rates calculated by multiplying the rate of the reaction catalyzed by cDNA-expressed enzymes (Vrec-CYPx) by the appropriate scaling factor, RAF.
b
Estimated per cent contribution of each isoform. Values in parentheses are the estimated per cent contribution of CYP2C19 and CYP3A4 calculated under the assumption that formation of 2,3-diOHCBZ is principally catalyzed by these two isoforms at a concentration of 10 μM 3-OHCBZ.