Regression analysis (r2) of the relationship between the rates of carbamazepine conversion to 2-and 3-hydroxycarbamazepine with the sample-to-sample variation in cytochrome P450 activity in human liver microsomes
| Enzymatic Reaction (Enzyme) | 3-Hydroxycarbamazepine | 2-Hydroxycarbamazepine | ||||||
|---|---|---|---|---|---|---|---|---|
| 30 μM2-a | 100 μM2-a | 300 μM2-a | 300 μM2-a | |||||
| r2 | P | r2 | P | r2 | P | r2 | P | |
| Phenacetin O-deethylation (CYP1A2) | 0.007 | >0.10 | 0.016 | >0.10 | 0.014 | >0.10 | 0.224 | >0.10 |
| Coumarin 7-hydroxylation (CYP2A6) | 0.456 | >0.10 | 0.352 | >0.10 | 0.362 | >0.10 | 0.206 | >0.10 |
| S-Mephenytion N-hydroxylation (CYP2B6) | 0.573 | <0.05 | 0.803 | <0.01 | 0.811 | <0.01 | 0.744 | <0.01 |
| Paclitaxel 6α-hydroxylation (CYP2C8) | 0.565 | <0.05 | 0.421 | >0.10 | 0.494 | >0.10 | 0.002 | >0.10 |
| Diclofenac 4′-hydroxylation (CYP2C9) | 0.002 | >0.10 | 0.004 | >0.10 | 0.010 | >0.10 | 0.100 | >0.10 |
| S-Mephenytoin 4′-hydroxylation (CYP2C19) | 0.002 | >0.10 | 0.001 | >0.10 | 0.001 | >0.10 | 0.078 | >0.10 |
| Bufurolol 1′-hydroxylation (CYP2D6) | 0.080 | >0.10 | 0.058 | >0.10 | 0.069 | >0.10 | 0.310 | >0.10 |
| Chlorzoxazone 6-hydroxylation (CYP2E1) | 0.009 | >0.10 | 0.014 | >0.10 | 0.107 | >0.10 | 0.034 | >0.10 |
| Testosterone 6β-hydroxylation (CYP3A4/5) | 0.475 | >0.10 | 0.477 | >0.10 | 0.457 | >0.10 | 0.011 | >0.10 |
| Lauric acid 12-hydroxylation (CYP4A9/11) | 0.014 | >0.10 | 0.081 | >0.10 | 0.101 | >0.10 | 0.040 | >0.10 |
Values in bold indicate significant correlations between P450 activity and rates of carbamazepine metabolite formation at P < 0.05.
r2, regression coefficient.
↵2-a Concentration of carbamazepine present in microsomal incubations.