TABLE 1.
Kinetic parameters for the metabolism of IFO and d4IFO by several human P450s
The Km and Vmax values for CYP3A4 were obtained by fitting the data shown in Fig. 3 to the Michaelis-Menten equation as described under Materials and Methods. Similar data and fits were produced and the same analyses were performed for each of the P450s indicated in this table. The reported values are averages that were determined from experiments performed in triplicate.
| IFO |
d4IFO |
|||||
|---|---|---|---|---|---|---|
| Vmaxa | Kma | Vmax/Km | Vmaxa | Kma | Vmax/Km | |
| pmol/min/pmol P450 | mM | min–1mM–1 | pmol/min/pmol P450 | mM | min–1mM−1 | |
| Activation | ||||||
| CYP2B6 | 3.8 ± 1 | 4.6 ± 2 | 0.8 | 4.1 ± 0.4 | 2.0 ± 0.4 | 2 |
| CYP2C9 | Trace amounts of acrolein formed | 0 | Trace amounts of acrolein formed | 0 | ||
| CYP2C19 | 1.0 ± 0.2 | 1.1 ± 0.6 | 0.9 | 1.0 ± 0.1 | 1.2 ± 0.4 | 0.8 |
| CYP3A4 | 0.7 ± 0.1 | 1.6 ± 0.6 | 0.4 | 0.4 ± 0.03 | 0.6 ± 0.12 | 0.7 |
| CYP3A5 | 0.1 ± 0.01 | 0.04 ± 0.03 | 2.5 | Not tested | N/A | |
| Inactivation | ||||||
| CYP2B6 | 0.4 ± 0.04 | 2.0 ± 0.4 | 0.2 | 0.2 ± 0.05 | 2.0 ± 0.8 | 0.1 |
| CYP2C9 | Trace amounts of CAA formed | 0 | Trace amounts of CAA formed | 0 | ||
| CYP2C19 | No CAA formed | 0 | No CAA formed | 0 | ||
| CYP3A4 | 0.14 ± 0.03 | 3.5 ± 1.7 | 0.04 | 0.05 ± 0.02 | 1.7 ± 1.2 | 0.03 |
| CYP3A5 | 0.02 ± 0.005 | 0.4 ± 0.3 | 0.05 | Not tested | N/A | |
a
Mean ± S.E.M.
N/A, CYP3A5 was not assessed for d4IFO metabolism.