TABLE 3

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
Contributionb
CYP2C19
CYP3A4
CYP2C19a
 CYP3A4a
 Total
Measured
CYP2C19
CYP3A4
CYP2C19
CYP3A4
Other
H003 2.6 33.9 1.2 6.8 8.0 5.6 0.12 0.98 10.7 89.3 0.0
H006 2.1 16.7 1.0 3.3 4.3 5.7 0.10 0.48 12.5 (16.6) 62.8 (83.3) 24.7
H023 3.6 19.8 1.7 3.9 5.6 4.8 0.16 0.57 22.0 78.0 0.0
H024 2.1 22.8 1.0 4.5 5.5 5.1 0.09 0.66 12.4 87.6 0.0
H030 19.1 48.9 9.0 9.7 18.7 16.5 0.86 1.42 37.7 62.3 0.0
H042 0.4 83.3 0.2 16.6 16.8 20.3 0.02 2.42 0.7 (0.8) 82.0 (99.2) 27.3
H056 28.6 29.4 13.5 5.9 19.4 14.7 1.29 0.85 60.1 39.9 0.0
H064 1.0 10.0 0.5 2.0 2.5 5.9 0.05 0.29 5.7 (13.6) 36.6 (86.4) 57.7
H088 10.1 27.2 4.8 5.4 10.2 9.6 0.46 0.79 36.6 63.4 0.0
H089 11.3 66.7 5.3 13.3 14.6 17.1 0.51 1.93 17.2 (20.1) 67.5 (79.1) 15.3
H093 2.3 9.4 1.1 1.9 3.0 4.7 0.10 0.27 17.6 (27.6) 46.2 (72.4) 36.2
H095 1.8 4.2 0.8 0.9 1.7 2.7 0.08 0.12 24.9 (39.6) 38.0 (60.4) 37.1
H103 1.3 15.6 0.6 3.1 3.7 7.4 0.06 0.45 5.6 (11.1) 44.5 (88.9) 49.9
H112
22.6
138.9
10.7
27.6
38.3
39.6
1.02
4.03
19.5 (20.2)
77.2 (79.8)
3.3

  • ↵ 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 percentage contribution of each isoform. Values in parentheses are the estimated percentage 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