TABLE 4

Kinetic parameters for 7-hydroxylation of racemic, S-, and R-warfarin by recombinant P450 2C enzymes and liver microsomes from marmosets, cynomolgus monkeys, and humans

Enzymes	Warfarin 7-Hydroxylation
Enzymes	R/S	K_m	V_max	V_max/K_m
		μM	min⁻¹	mM min⁻¹
Marmoset P450 2C19	Racemic	12 ± 1	0.04 ± 0.01	3.3 ± 0.9
	S	14 ± 1	0.20 ± 0.01	14 ± 1
	R	755 ± 84	0.20 ± 0.02	0.26 ± 0.04
Cynomolgus monkey P450 2C19	Racemic	37 ± 5	2.5 ± 0.1	68 ± 10
	S	124 ± 27	1.3 ± 0.1	10 ± 2
	R	51 ± 6	7.0 ± 0.2	137 ± 17
Human P450 2C9	Racemic	22 ± 8	0.018 ± 0.001	0.82 ± 0.30
	S	3.1 ± 0.1	0.17 ± 0.02	55 ± 2
	R	123 ± 35	0.007 ± 0.001	0.057 ± 0.018
MLM	Racemic	150 ± 39	0.0014 ± 0.0002	0.0093 ± 0.0028
	S	9.5 ± 1.6	0.0058 ± 0.0003	0.61 ± 0.11
	R	240 ± 55	0.0037 ± 0.0005	0.015 ± 0.004
CLM	Racemic	44 ± 2	0.0033 ± 0.0001	0.075 ± 0.004
	S	73 ± 6	0.0051 ± 0.0002	0.070 ± 0.006
	R	16 ± 3	0.0059 ± 0.0003	0.37 ± 0.07
HLM	Racemic	7.7 ± 0.3	0.0016 ± 0.0001	0.21 ± 0.02
	S	5.0 ± 0.3	0.0028 ± 0.0001	0.56 ± 0.04
	R	237 ± 22	0.0016 ± 0.0001	0.0068 ± 0.008

CLM, cynomolgus monkey liver microsomes; HLM, human liver microsomes; MLM, marmoset liver microsomes.