TABLE 2

Metabolism of IFO and d4IFO by the polymorphic variants of CYP2B6 and CYP2C9

The data shown in Fig. 4 are summarized here. Data are expressed as metabolite formation in pmol/min per picomole of P450, and the metabolite production compared with wild-type metabolite production in terms of fold change. Also, the percent increase or decrease of the metabolite produced from d4IFO compared with IFO is given. The data were determined in triplicate. Statistical significance was determined using the unpaired t test in Prism 6 (GraphPad Inc.).

IFOd4IFOIncrease in Active Metabolite over IFO
Acrolein ProducedaFold Change over Wild-TypeAcrolein ProducedaFold Change over Wild Type
pmol/min/pmol P450pmol/min/pmol P450%
Activation
CYP2B6*10.5 ± 0.061.01.1 ± 0.08*1.0120.0
CYP2B6*40.1 ± 0.020.20.2 ± 0.02††0.2100.0
CYP2B6*60.3 ± 0.10.60.3 ± 0.08††0.30.0
CYP2B6*71.7 ± 0.05†††3.43.6 ± 0.04†††**3.3111.8
CYP2B6*91.6 ± 0.3†††3.22.5 ± 0.3††2.356.3
CYP2C9*10.05 ± 0.011.00.05 ± 0.021.00.0
CYP2C9*20.2 ± 0.14.00.5 ± 0.05††10.0150.0
CYP2C9*30 ± 00.00.2 ± 0.044.0N/A
IFOd4IFODecrease in Inactive Metabolite over IFO
CAA ProducedaFold Change over Wild TypeCAA ProducedaFold Change over Wild Type
pmol/min/pmol P450pmol/min/pmol P450%
Inactivation
CYP2B6*10.1 ± 0.021.00.06 ± 0.021.040.0
CYP2B6*40.04 ± 0.0010.40 ± 0*0.0100.0
CYP2B6*60.02 ± 0.010.20 ± 00.0100.0
CYP2B6*70 ± 00.00 ± 00.0N/A
CYP2B6*90.02 ± 0.010.20 ± 00.0100.0
CYP2C9*10.01 ± 0.0031.00 ± 01.0100.0
CYP2C9*20 ± 00.00 ± 00.0N/A
CYP2C9*30 ± 00.00 ± 00.0N/A
  • P < 0.05, ††P < 0.01, †††P, 0.005 for comparisons within polymorphic variants

  • * P < 0.01, **P < 0.005 for comparisons between IFO and d4IFO

  • a Mean ± S.E.M.

  • N/A no metabolite was detected with IFO, therefore percent change could not be calculated.