Kinetic parameters of 4′-hydroxymephenytoin formation in genotyped HLMs
Four to five human liver samples per CYP2C19 genotype were used, and S-mephenytoin to 4′-hydroxymephenytoin conversion was measured. S-mephenytoin (2.86–366.4 μM) was incubated with 0.5 mg/ml HLMs and 1 mM NADPH in 100 μl incubation mixture for 45 minutes at 37°C. A single-site Michaelis-Menten model was used to describe kinetics data. The “null” refers to CYP2C19*2 or *4 allele.
| CYP2C19*17/*17 | *1/*17 | *1/*1 | *17/null | *1/null | null/null | |
|---|---|---|---|---|---|---|
| N | 5 | 5 | 5 | 5 | 5 | 4 |
| Km (µM) | 48.9 | 50.7 | 62.9 | 50.4 | 72.7 | 139.5 |
| Km S.D. | 18.2 | 30.4 | 19.7 | 15.8 | 11.8 | 12.7 |