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.

IFOd4IFO
VmaxaKmaVmax/KmVmaxaKmaVmax/Km
pmol/min/pmol P450mMmin–1mM–1pmol/min/pmol P450mMmin–1mM−1
Activation
CYP2B63.8 ± 14.6 ± 20.84.1 ± 0.42.0 ± 0.42
CYP2C9Trace amounts of acrolein formed0Trace amounts of acrolein formed0
CYP2C191.0 ± 0.21.1 ± 0.60.91.0 ± 0.11.2 ± 0.40.8
CYP3A40.7 ± 0.11.6 ± 0.60.40.4 ± 0.030.6 ± 0.120.7
CYP3A50.1 ± 0.010.04 ± 0.032.5Not testedN/A
Inactivation
CYP2B60.4 ± 0.042.0 ± 0.40.20.2 ± 0.052.0 ± 0.80.1
CYP2C9Trace amounts of CAA formed0Trace amounts of CAA formed0
CYP2C19No CAA formed0No CAA formed0
CYP3A40.14 ± 0.033.5 ± 1.70.040.05 ± 0.021.7 ± 1.20.03
CYP3A50.02 ± 0.0050.4 ± 0.30.05Not testedN/A
  • a Mean ± S.E.M.

  • N/A, CYP3A5 was not assessed for d4IFO metabolism.