TABLE 4

ISEF determined based on metabolite formation and comparison with ISEF determined using substrate depletion

P450Probe SubstrateHLMrhP450ISEF (Metabolite Formation)ISEF (Substrate Depletion): ISEF-CLintc
VmaxKmVmaxKmVISEFaCLISEFb
pmol per min/mgμMpmol per min/pmol P450μM
1A2Phenacetin5114752340.190.140.17
2C9Diclofenac160917.7299.70.760.420.54
2D6Bufuralol13511528.30.320.230.15
3A4Midazolam9732.94212.890.330.320.21
  • a VISEF-calculated on the basis of Vmax (eq. 1).

  • b CLISEF-calculated on the basis of CLint = Vmax/Km (eq. 2).

  • c ISEF-CLint calculated on the basis of measured substrate depletion, CLint (eq. 3).