TABLE 4

Experimentally determined IC₅₀ values for various metabolism-dependent inhibitors of human liver microsomal P450 enzymes with and without a 10-fold dilution based on the initial and final concentrations of inhibitor

[Initial] refers to processing the IC₅₀ values based on an initial or predilution concentration of inhibitor, whereas [Final] refers to processing the IC₅₀ values based on a final or postdilution concentration.

P450 Enzyme	Substrate	Inhibitor	IC₅₀
			No Dilution		With 10-Fold Dilution			Perloff et al. (2009)^{^c}			Obach et al. (2007)^{^c}
			Without NADPH	With NADPH	Without NADPH	With NADPH		Without NADPH	With NADPH		Without NADPH	With NADPH
			Without NADPH	With NADPH	[Final]	[Initial]	[Final]	[Final]	[Initial]^{^b}	[Final]	[Final]	[Initial]^{^b}	[Final]
		μM
CYP1A2	Phenacetin	Furafylline	9.6	0.28	3.4	0.36	0.036	8.4	0.21	0.021	1.5	0.27	0.027
CYP2B6	Bupropion	Ticlopidine	0.18	0.047	0.20	0.39	0.039	0.84	0.48	0.048	0.13	0.31	0.031
CYP2C8	Amodiaquine	Gemfibrozil glucuronide	32	2.1	27	2.8	0.28	26	4.6	0.46	N.D.	N.D.	N.D.
CYP2C9	Diclofenac	Tienilic acid	1.0	0.066	0.92	0.57	0.057	1.7	0.49	0.049	0.43	0.27	0.027
CYP2C19^{^a}	S-Mephenytoin	S-Fluoxetine	93	5.3	61	14	1.4	85	15.5	3.1	N.D.	N.D.	N.D.
CYP2D6	Dextromethorphan	Paroxetine	0.73	0.05	1.5	0.53	0.053	1.1	0.66	0.066	0.23	0.12	0.012
CYP3A4	Midazolam	Azamulin	0.21	0.038	0.34	0.31	0.031	0.15	0.025	0.0025	N.D.	N.D.	N.D.
CYP3A4	Testosterone	Azamulin	0.90	0.095	0.46	0.44	0.044	0.098	0.077	0.0077	N.D.	N.D.	N.D.
CYP3A4	Midazolam	Diltiazem	89	18	78	12	1.2	100	34	3.4	54	37	3.7
CYP3A4	Testosterone	Diltiazem	170	32	138	22	2.2	130	28	2.8	55	18	1.8
CYP3A4	Midazolam	Erythromycin	73	13	84	25	2.5	N.D.	N.D.	N.D.	18	12	1.2
CYP3A4	Midazolam	Methimazole	570	80	510	76	7.6	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
CYP3A4	Midazolam	Mibefradil	0.93	0.027	0.46	0.61	0.061	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
CYP3A4	Midazolam	Mifepristone	15	0.53	6.9	0.69	0.069	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
CYP3A4	Midazolam	Troleandomycin	23	0.85	12.3	0.63	0.063	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
CYP3A4	Midazolam	Verapamil	25	7.1	25	4.1	0.41	25	3.4	0.34	12	1.2	0.12
CYP3A4	Testosterone	Verapamil	34	3.0	29	3.8	0.38	28	2.7	0.27	8.2	1.5	0.15

N.D., no data.
↵a A dilution factor of 5-fold was used by Perloff et al. (2009).
↵b Calculated on the basis of the reported fold dilution.
↵c Values published by these authors.