TABLE 2

Kinetic parameters for metabolism of dextromethorphan, midazolam, phenytoin, and tolbutamide in rat liver microsomes and freshly isolated hepatocytes Data are expressed as the mean of n = 3 (microsomes) and n = 4 (hepatocytes) ± S.D.

In Vitro System	Pathway	V_max	K_M	S₅₀	Hill Coefficient	K_i,s	CL_int
		nmol/min	μM	μM	n	μM	μl/min
Microsomes	Dextrorphan	0.53 ± 0.04^a,^b	0.42 ± 0.01^b			448 ± 142	1246 ± 86^a,^b
		0.97 ± 0.18^a,^c	75 ± 12^c				13.4 ± 4.6^a,^c
	3-Methoxymorphinan	1.30^a		65			21.5 ± 9.3^a,^d
	1-Hydroxymidazolam	0.58 ± 0.07^a		11 ± 2	1.37 ± 0.17		29 ± 5^a,^d
	4-Hydroxymidazolam	0.89 ± 0.17^a		9 ± 4	1.76 ± 0.17		50 ± 22^a,^d
	5-(4-Hydroxyphenyl)-	0.027 ± 0.009^a	3.21 ± 0.56				8.40 ± 2.75^a,^b
	5-Phenylhydantoin						0.18 ± 0.06^a,^c
	4-Hydroxytolbutamide^e	4.2^a	710				5.91^a
Hepatocytes	Dextrorphan	0.08 ± 0.02^b,^f	0.15 ± 0.03^b			645 ± 188	545 ± 50^b,^f
		0.48 ± 0.11^c,^f	10 ± 3.6^c				49 ± 9^c,^f
	3-Methoxymorphinan	0.84^f		25			31.3 ± 6.1^c,^f
	1-Hydroxymidazolam	0.28 ± 0.10^f	18 ± 6				16 ± 7^f
	4-Hydroxymidazolam	0.17 ± 0.10^f	15 ± 7				12 ± 7^f
	5-(4-Hydroxyphenyl)-	0.22 ± 0.05^f	5.23 ± 1.38				43.3 ± 7.4^b,^f
	5-Phenylhydantoin						0.39 ± 0.27^c,^f
	4-Hydroxytolbutamide^e	0.74^f	650				1.14^f

↵ a Values expressed per milligram protein.
↵ b Data for the high-affinity, low-capacity site.
↵ c Data for the low-affinity, high-capacity site.
↵ d CL_max (maximal clearance).
↵ e Tolbutamide data taken from Ashforth et al. (1995).
↵ f Values expressed per 10⁶ cells.