TABLE 2

Kinetic parameters for the rCYP3A4- and rCYP3A5-catalyzed metabolism of MDZ, TST, terfenadine, and vincristine

Data are presented as the mean ± S.D. (n = 3 determinations), except for the CYP3A5/CYP3A4 V_max/K_m (S₅₀) ratio.

P450	Substrate	Model	K_m (S₅₀)	V_max^{^a}	n^{^b}	V_max/K_m(S₅₀)	V_max/K_m (S₅₀) Ratio^{^c}
			µM
CYP3A4	MDZ	Hyperbolic	1.8 ± 0.3	19 ± 1	—	11.0
	TST	Sigmoidal	78 ± 34	86 ± 3	1.2 ± 0.13	1.1
	Terfenadine	Hyperbolic	3.4 ± 0.4	24 ± 2	—	7
	Vincristine	Sigmoidal	75 ± 22	15 ± 4	1.5 ± 0.15	0.2
CYP3A5	MDZ	Hyperbolic	3.0 ± 0.5	35 ± 2	—	11.7	1.1
	TST	Hyperbolic	67 ± 13	56 ± 4	—	0.8	0.7
	Terfenadine	Hyperbolic	1.5 ± 0.2	18 ± 1	—	12.0	1.7
	Vincristine	Sigmoidal	47 ± 6.7	70 ± 7	1.5 ± 0.11	1.5	7.5

↵^a Presented as pmol/min/pmol P450, except for the formation of vincristine M1 metabolite. No attempt was made to formally quantitate M1, so data are presented as arbitrary units (see Materials and Methods).
↵^b Hill coefficient.
↵^c Ratio of CYP3A5 V_max/K_m (S₅₀) versus CYP3A4 V_max/K_m (S₅₀).