Table 3

Enzyme kinetics measured for reactions catalyzed by CYP2D6 isoforms in vitro; dextromethorphan O-demethylation, dextromethorphanN-demethylation, codeine O-demethylation, and fluoxetine N-demethylation products were measured

Reaction	P450 Isoform	K_m	V_max	V/K	Normalized V/K Ratio
		mM	pmol/pmol P450/min	ml/pmol P450/min
DextromethorphanO-demethylation	CYP2D6.1	3.04 ± 0.64	9.0 ± 0.50	2.96	1
	CYP2D6.2	26.3 ± 1.64	14.6 ± 0.3	0.56	0.19
	CYP2D6.10	92.1 ± 13.5	2.6 ± 0.2	0.028	0.01
	CYP2D6.17	30.7 ± 2.34	8.6 ± 0.2	0.28	0.10
Dextromethorphan N-demethylation	CYP2D6.1	1300 ± 800	39 ± 10	0.03	1
	CYP2D6.2	2600 ± 700	56 ± 9	0.023	0.77
	CYP2D6.10	3500 ± 200	48 ± 2	0.014	0.47
	CYP2D6.17	1000 ± 500	11 ± 2	0.01	0.33
CodeineO-demethylation	CYP2D6.1	190 ± 30	6.40 ± 0.25	0.034	1
	CYP2D6.2	480 ± 50	5.68 ± 0.17	0.012	0.35
	CYP2D6.10	N.D.		N.D.	N.D.
	CYP2D6.17	860 ± 220	1.70 ± 0.17	0.002	0.06
Fluoxetine N-demethylation	CYP2D6.1	2.84 ± 0.35	0.653 ± 0.024	0.23	1
	CYP2D6.2	4.33 ± 0.36	0.257 ± 0.007	0.059	0.26
	CYP2D6.10	13.4 ± 1.90	0.056 ± 0.003	0.004	0.02
	CYP2D6.17	8.31 ± 0.30	0.281 ± 0.003	0.034	0.15

All reactions were run in duplicate. Error estimates are based on the best fit of the average values obtained at each point to the Michaelis-Menten equation using nonlinear regression analysis.

N.D., none detectable.