TABLE 2

Regression analysis (r2) of the relationship between the rates of 3-OHCBZ conversion to 2,3-diOHCBZ with the sample-to-sample variation in cytochrome P450 activity in human liver microsomes Values in bold indicate significant correlations between P450 activity and residual activity for CBZ metabolites at P < 0.05.

Enzymatic Reaction (Enzyme)
10 μM 3-OHCBZa
2,3-diOHCBZ Formation 100 μM 3-OHCBZa
100 μM 3-OHCBZa + TAOb
r2
P
r2
P
r2
P
Phenacetin O-deethylation (CYP1A2) 0.013 0.698 0.008 0.759 0.391 0.017
Coumarin 7-hydroxylation (CYP2A6) 0.006 0.789 0.002 0.867 >0.001 0.972
S-Mephenytoin N-hydroxylation (CYP2B6) 0.593 0.001 0.687 <0.001 0.104 0.259
Paclitaxel 6α-hydroxylation (CYP2C8) 0.171 0.141 0.174 0.138 0.014 0.683
Diclofenac 4′-hydroxylation (CYP2C9) 0.099 0.272 0.047 0.457 0.102 0.265
S-Mephenytoin 4′-hydroxylation (CYP2C19) 0.424 0.012 0.227 0.085 0.893 <0.001
Bufuralol 1′-hydroxylation (CYP2D6) 0.098 0.273 0.069 0.365 0.082 0.321
Chlorzoxazone 6-hydroxylation (CYP2E1) 0.240 0.075 0.283 0.051 0.141 0.185
Testosterone 6β-hydroxylation (CYP3A4/5) 0.929 <0.001 0.949 <0.001 0.260 0.059
Lauric acid 12-hydroxylation (CYP4A9/11)
0.097
0.277
0.030
0.554
0.317
0.036

  • r2, regression coefficient

  • ↵ a Concentration of 3-OHCBZ present in microsomal incubations

  • ↵ b Microsomes preincubated for 20 min with TAO (100 μM)