Table 6

Inhibition of human cytochrome P450 enzymes CYP1A2, CYP2C9, CYP2E1, and CYP3A by Org OD14, Org 4094, Org 30126, Org OM38, and enzyme-selective inhibitors^6-a

Cytochrome P450	Inhibitor	Type of Inhibition	K_m	V_max^6-a	K_i
			μM	pmol/min/mg	μM
CYP1A2	None	None	0.25 ± 0.03	118 ± 4
	Org OD14	Competitive			100
	Org 4094	Competitive			245
	Org 30126	Competitive			640
	Org OM38	Competitive			775
	Fluvoxamine	Noncompetitive	0.33 ± 0.04	126 ± 6	0.21 ± 0.02
CYP2C9	None	None	12.6 ± 0.8	3178 ± 65
	Org OD14	Competitive	12.3 ± 1.2	3089 ± 94	14.8 ± 1.7
	Org 4094	Competitive	12.2 ± 1.1	3081 ± 86	17.4 ± 1.9
	Org 30126	Competitive	13.1 ± 0.9	3168 ± 64	84.2 ± 14.3
	Org OM38	Competitive	12.8 ± 1.4	3256 ± 108	32.9 ± 5.3
	Sulfaphenazole	Competitive	14.3 ± 2.2	3283 ± 161	0.28 ± 0.05
CYP2E1	None	None	238 ± 29	2047 ± 119
	Diethyldithiocarbamate	Noncompetitive	230 ± 18	1990 ± 74	33.0 ± 2.6
CYP3A	None	None	62.7 ± 8.1	9464 ± 393
	Org OD14	Competitive	62.5 ± 8.0	9490 ± 396	14.5 ± 2.0
	Org 4094	Competitive	61.8 ± 7.1	9474 ± 350	3.57 ± 0.39
	Org 30126	Competitive	63.3 ± 7.0	9557 ± 347	6.05 ± 0.67
	Org OM38	Noncompetitive	56.3 ± 9.7	4727 ± 331	62.8 ± 8.8
	0.05 μM ketoconazole	Competitive^6-b	64.0 ± 9.1	9569 ± 449	0.017 ± 0.003
	0.2 μM ketoconazole	Competitive^6-b	65.7 ± 8.3	9683 ± 410	0.020 ± 0.003

Results are presented as means ± S.D.

↵6-a K_m andV_max values given for incubations in the presence of Org OD14, Org 4095, Org 30126, Org OM38, or a model inhibitor represent back-calculated values in the EZ-FIT curve-fitting program and are only indicative of a goodness of fit.
↵6-b The best fit for ketoconazole was obtained with the competitive inhibition model. However, data showed that the metabolism of testosterone in the presence of ketoconazole has a sigmoidal nature. Therefore, the type of CYP3A4 inhibition by ketoconazole is not clear.