Kinetics of losartan oxidation in different CYP2C9 genotypes
| Genotype | n | A | B | ||
|---|---|---|---|---|---|
| pmol of E-3174/mg of protein/min | Km | Vmax | Vmax/Km | ||
| CYP2C93-1501/3-1501 | 9 | 3.4 ± 1.2 | 4.4 ± 1.4 | 33.5 ± 18.3 | 7.4 ± 2.8 |
| CYP2C93-1501/3-1502 | 5 | 2.7 ± 0.9 | 7.6 ± 4.3 | 33.9 ± 9.7 | 5.2 ± 1.8 |
| CYP2C93-1501/3-1503 | 4 | 1.2 ± 0.83-160 | 6.3 ± 1.0 | 16.8 ± 9.5 | 2.7 ± 1.63-160 |
| CYP2C93-1502/3-1502 | 4 | 1.6 ± 1.03-150 | 5.4 ± 0.9 | 24.5 ± 14.3 | 4.3 ± 2.2 |
| CYP2C93-1502/3-1503 | 2 | 1.6, 4.5 | 4.2, 6.2 | 17.0, 39.6 | 2.7, 9.4 |
| CYP2C93-1503/3-1503 | 1 | 0.4 | 5.1 | 2.1 | 0.4 |
A, the formation rate of E-3174 from losartan (0.5 μM) in liver microsomes from subjects of different CYP2C9 genotypes. Experiments were carried out in the absence of P450 inhibitors. B,Km (μM) and Vmax (pmol/mg of protein/min) of E-3174 formation from losartan in human liver microsomes with different CYP2C9 genotypes in the presence of the specific CYP3A4 inhibitor TAO (10 μM).