Table 2

Michaelis constants determined using product formation measurements and substrate depletion measurements for six P450 substrates

Substrate	P450	Reaction	K_M
Substrate	P450	Reaction	Product Formation^2-b	Substrate Depletion^2-b
			μM
Tacrine	CYP1A2	1-Hydroxylation^2-a	2.8	1.4
Diclofenac	CYP2C9	4′-Hydroxylation	3.1	3.3
Imipramine	CYP2C19	N-Demethylation	22	9.8
Dextromethorphan	CYP2D6	O-Demethylation	0.44	0.30
Thioridazine	CYP2D6	S-Oxidation	0.12	0.12
Midazolam	CYP3A4	1′-Hydroxylation^2-a	1.0	0.52

↵2-a Reaction monitored in product formation experiments. Tacrine 2- and 4′-hydroxylation was also observed but product formed was less than the lower limit of quantitation. Midazolam 4-hydroxylation was also observed with aK_M of 15 μM.
↵2-b Product formationK_M values represent the mean of three determinations, substrate depletion the average of two determinations.