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.).

	IFO		d4IFO		Increase in Active Metabolite over IFO
	Acrolein Produceda	Fold Change over Wild-Type	Acrolein Produceda	Fold Change over Wild Type
	pmol/min/pmol P450		pmol/min/pmol P450		%
Activation
CYP2B6*1	0.5 ± 0.06	1.0	1.1 ± 0.08*	1.0	120.0
CYP2B6*4	0.1 ± 0.02†	0.2	0.2 ± 0.02††	0.2	100.0
CYP2B6*6	0.3 ± 0.1	0.6	0.3 ± 0.08††	0.3	0.0
CYP2B6*7	1.7 ± 0.05†††	3.4	3.6 ± 0.04†††**	3.3	111.8
CYP2B6*9	1.6 ± 0.3†††	3.2	2.5 ± 0.3††	2.3	56.3
CYP2C9*1	0.05 ± 0.01	1.0	0.05 ± 0.02	1.0	0.0
CYP2C9*2	0.2 ± 0.1	4.0	0.5 ± 0.05††	10.0	150.0
CYP2C9*3	0 ± 0	0.0	0.2 ± 0.04	4.0	N/A
	IFO		d4IFO		Decrease in Inactive Metabolite over IFO
	CAA Produceda	Fold Change over Wild Type	CAA Produceda	Fold Change over Wild Type
	pmol/min/pmol P450		pmol/min/pmol P450		%
Inactivation
CYP2B6*1	0.1 ± 0.02	1.0	0.06 ± 0.02	1.0	40.0
CYP2B6*4	0.04 ± 0.001	0.4	0 ± 0*	0.0	100.0
CYP2B6*6	0.02 ± 0.01	0.2	0 ± 0	0.0	100.0
CYP2B6*7	0 ± 0†	0.0	0 ± 0	0.0	N/A
CYP2B6*9	0.02 ± 0.01	0.2	0 ± 0	0.0	100.0
CYP2C9*1	0.01 ± 0.003	1.0	0 ± 0	1.0	100.0
CYP2C9*2	0 ± 0	0.0	0 ± 0	0.0	N/A
CYP2C9*3	0 ± 0	0.0	0 ± 0	0.0	N/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

^aMean ± S.E.M.

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