TABLE 4

Absolute IC₅₀ values of standard inhibitors for nine major P450 enzymes determined in MMHHs and CHHs and their corresponding fold difference values

P450 Isoform	Maker Reaction	Inhibitors	Absolute IC₅₀		Fold Difference MMHH/CHH
P450 Isoform	Maker Reaction	Inhibitors	MMHH	CHH	Fold Difference MMHH/CHH
			µM	µM
1A2	Phenacetin O-deethylation	Fluvoxamine	0.007	0.025	0.28^{^a}
		Furafylline	0.81	1.2	0.67
		Methoxsalen	0.015	0.025	0.60
		α-Naphthoflavone	0.029	0.047	0.62
		Propranolol	0.57	0.39	1.46
2A6	Coumarin hydroxylation	Ketoconazole	91.4	100	0.91
		Methoxsalen	0.10	0.03	3.33^{^a}
		Phenelzine	2.1	2.0	1.07
		Tranylcypromine	0.059	0.007	8.43^{^a}
2B6	Bupropion hydroxylation	Ketoconazole	2.7	3.8	0.72
		Methoxsalen	4.5	5.9	0.76
		Phenelzine	11.2	5.6	2.01
		PPP	4.8	5.5	0.87
		Thiotepa	4.3	17.7	0.24^{^a}
		Ticlopidine	22.4	12.3	1.82
2C8	Amodiaquine N-deethylation	Ketoconazole	11.9	10.2	1.17
		Methoxsalen	>100	>100	NC
		Montelukast	4.1	4.3	0.95
		Tranylcypromine	77.8	58	1.35
2C9	Diclofenac hydroxylation	Fluconazole	23.2	82.0	0.28^{^a}
		Ketoconazole	7.2	13.0	0.55
		Methoxsalen	34.2	36.7	0.93
		Sulfaphenazole	0.4	0.63	0.59
2C19	Mephenytoin hydroxylation	Fluconazole	4.6	3.2	1.46
		Fluoxetine	1.2	4.8	0.24^{^a}
		Fluvoxamine	0.02	0.04	0.64
		Methoxsalen	14.5	12.1	1.19
		Omeprazole	4.6	2.6	1.80
		Ticlopidine	13.8	20.1	0.69
2D6	Dextromethorphan O-demethylation	Cinacalcet	3.3	11.5	0.29^{^a}
		Fluoxetine	0.63	0.92	0.68
		Methoxsalen	39.6	43.1	0.92
		Paroxetine	0.37	0.75	0.49
		Propafenone	0.08	0.07	1.14
		Quinidine	0.04	0.02	2.33
2 E1	Chlorzoxazone hydroxylation	Methoxsalen	75.7	81.5	0.93
		Methylpyrazole	1.4	1.1	1.24
3A4	Midazolam hydroxylation	Erythromycin	5.3	4.1	1.31
		Ketoconazole	0.09	0.09	1.11
		Methoxsalen	>100	>100	NC
		Mibefradil	0.32	0.32	1.00
		Troleandomycin	2.2	1.1	1.98
		Verapamil	18.8	5.97	3.15^{^a}
3A4	Testosterone hydroxylation	Erythromycin	13.9	22.4	0.62
		Ketoconazole	0.045	0.12	0.38
		Methoxsalen	10.3	29.8	0.35
		Mibefradil	0.25	0.75	0.33
		Troleandomycin	3.0	7.4	0.40
		Verapamil	4.4	8.8	0.50

NC, fold difference not calculated; PPP, 2-phenyl-2-(1-piperidinyl)propane.
↵^a Fold difference of ≥3 or ≤0.3 between MMHHs and CHHs.