TABLE 7

Summary of enzyme kinetic parameters (Mean ± S.E.) for 12 human cytochrome P450 activities in pooled human liver microsomes and recombinant heterologously expressed P450 enzymes

Enzyme	Assay	Pooled Human Liver Microsomes					Recombinant Heterologously Expressed Enzyme
Enzyme	Assay			Kinetic mechanism	K_m	V_max	Kinetic mechanism	K_m	V_max
			μM	pmol/mg/min		μM	pmol/pmol
							P450/min
CYP1A2	Phenacetin O-deethylase	Simple	47.0 ± 1.9	688 ± 10	Simple	16.7 ± 0.9	31.3 ± 0.7
CYP2A6	Coumarin 7-hydroxylase	Simple	0.841 ± 0.037	940 ± 10	Simple	0.826 ± 0.037	12.4 ± 0.2
CYP2B6	Bupropion hydroxylase	Simple	81.7 ± 1.3	413 ± 2	Simple	66.8 ± 1.4	12.9 ± 0.1
CYP2C8	Amodiaquine N-deethylase	Simple	1.89 ± 0.06	1480 ± 20	Simple	0.728 ± 0.040	11.2 ± 0.2
CYP2C9	Diclofenac 4′-hydroxylase	Simple	4.04 ± 0.12	1670 ± 20	Simple	0.589 ± 0.020	14.9 ± 0.1
CYP2C9	Tolbutamide hydroxylase	Simple	147 ± 4	276 ± 3	Simple	82.0 ± 2.5	11.9 ± 0.1
CYP2C19	(S)-Mephenytoin 4′-hydroxylase	Simple	57.2 ± 2.2	58.3 ± 0.8	Simple	17.3 ± 0.5	8.76 ± 0.07
CYP2D6	Dextromethorphan O-demethylase	Simple	4.64 ± 0.21	202 ± 3	Simple	0.196 ± 0.003	5.84 ± 0.02
CYP2E1	Chlorzoxazone 6-hydroxylase	Simple	73.9 ± 2.2	2360 ± 20	Simple	135 ± 5	27.3 ± 0.4
CYP3A	Felodipine dehydrogenase	Substrate inhibition	2.81 ± 0.61	1630 ± 180	Substrate inhibition	0.938 ± 1.137^a	36.8 ± 3.0^a
					Substrate inhibition	1.41 ± 0.17^b	24.2 ± 2.0^b
CYP3A	Midazolam 1′-hydroxylase	Substrate inhibition	2.27 ± 0.18	1220 ± 40	Substrate inhibition	0.622 ± 0.025^a	16.3 ± 0.3^a
					Substrate inhibition	1.53 ± 0.09^b	54.6 ± 1.8^b
CYP3A	Testosterone 6β-hydroxylase	Simple	46.4 ± 1.9	5260 ± 80	Substrate inhibition	31.4 ± 2.5^a	210 ± 9^a
					Substrate inhibition	106 ± 13^b	164 ± 12^b

↵a Mean ± S.E. for recombinant CYP3A4
↵b Mean ± S.E. for recombinant CYP3A5