TABLE 2

Metabolic parameters of raloxifene glucuronidation by liver and intestinal microsomes in human and rat Raloxifene was added to the microsomes with cofactors as described under Materials and Methods. Apparent K_m, V_max, and CL_int values were obtained by nonlinear regression of the data points in Fig. 4 and Fig. 6.

Species	Glucuronide	Site	Apparent K_m (K_si)^a	Apparent V_max	Apparent CL_int
			μM	pmol/min/mg	μl/min/mg
Human	M1	Liver^b	14.48	1183	82
		Jejunum^b	4.89	348	71
		Ileum^b	8.72	424	49
	M2	Liver^b	3.63	747	206
		Jejunum^b	3.68	3711	1008
		Ileum^b	4.88	3871	793
Rat	M1	Liver^b	3.04	603	199
		Duodnum^c	2.42 (26.00)^a	750	309
		Jejunum^c	1.40 (44.31)^a	419	300
		Ileum^c	0.95 (47.80)^a	117	124
		Colon^c	0.85 (74.27)^a	145	170
	M2	Liver^b	4.39	161	37
		Duodnum^c	13.98 (4.76)^a	678	49
		Jejunum^c	11.93 (6.09)^a	368	31
		Ileum^c	3.518 (23.83)^a	39	11
		Colon^b	0.77	23	30

↵ a The constant describing the substrate inhibition interaction (K_si) was calculated according to eq. 3 as described under Materials and Methods
↵ b The parameters were calculated from the data up to 34.7 μM raloxifene using the Michaelis-Menten equation
↵ c The parameters were calculated according to eq. 3 as described under Materials and Methods since it showed substrate inhibition (see Results)