Correlation between the formation rate of pactimibe metabolites and different P450 marker activities in human hepatic microsomes (n = 16) Final protein concentration, substrate concentration, and reaction time were set at 1 mg/ml, 100 μM, and 30 min, respectively.
P450 Isoforms | Marker Reaction | Correlation (r2) | ||
|---|---|---|---|---|
| M-1 formation | R-125528 formation | |||
| CYP 1A2 | 7-Ethoxyresorufin O-dealkylation | 0.019 | 0.025 | |
| CYP 2A6 | Coumarin 7-hydroxylation | 0.0018 | 0.01 | |
| CYP 2B6 | S-Mephenytoin N-demethylation | 0.25 | 0.23 | |
| CYP 2C8 | Paclitaxel 6α-hydroxylation | 0.54 | 0.45 | |
| CYP 2C9 | Diclofenac 4′-hydroxylation | 0.18 | 0.065 | |
| CYP 2C19 | S-Mephenytoin 4′-hydroxylation | 0.18 | 0.08 | |
| CYP2D6 | Dextromethorphan O-demethylation | 0.52 | 0.022 | |
| CYP2E1 | Chlorzoxazone 6-hydroxylation | 0.015 | 0.0022 | |
| CYP3A4/5 | Testosterone 6β-hydroxylation | 0.27 | 0.86 | |
| CYP4A9/11 | Lauric acid 12-hydroxylation | 0.04 | 0.062 | |