Table 4

Enzyme kinetic parameters of sulfation and glucuronidation for the four stereoisomers of troglitazone with rat liver

Conjugation	Parameter	Stereoisomer^3-a
Conjugation	Parameter	SS	SR	RS	RR
Sulfation	f _u ^3-b	0.0208		0.0257
	V _max (nmol/min/mg protein)	0.961 ± 0.154	1.07 ± 0.13	0.0548 ± 0.0033	0.0567 ± 0.0026
	K _m (μM)^3-c	0.0256 ± 0.0059	0.0294 ± 0.0049	0.00597 ± 0.00115	0.00534 ± 0.00087
	K _i (μM)^3-d	0.0543 ± 0.0131	0.0704 ± 0.0131	1.12 ± 0.55	3.91 ± 4.68
	CLu _int (ml/min/mg protein)^3-e	37.5 ± 10.5	36.4 ± 7.5	9.18 ± 1.85	10.6 ± 1.8
	V _max (nmol/min/g liver)^3-f	48.7	54.2	2.78	2.85
	CLu _int (ml/min/g liver)^3-f	1,900	1,850	466	532
	CLu _int(ml/min/kg)^3-g	76,000	74,000	18,700	21,300
	Mean CLu _int(ml/min/kg)^3-h	47,500

Glucuronidation	f _u ^3-j	0.0100		0.0100
	V _max (nmol/min/mg protein)	1.57 ± 1.40	0.940 ± 0.068	0.358 ± 0.130	0.346 ± 0.120
	K _m (μM)^3-c	1.13 ± 1.10	0.291 ± 0.025	0.695 ± 0.282	0.683 ± 0.263
	CLu _int (ml/min/mg protein)^3-e	1.39 ± 1.83	3.23 ± 0.36	0.515 ± 0.280	0.507 ± 0.263
	V _max(nmol/min/g liver)^3-j	71.3	42.7	16.3	15.7
	CLu _int (ml/min/g liver)^3-j	63.1	147	23.4	23.0
	CLu _int(ml/min/kg)^3-g	2,520	5,870	935	921
	MeanCLu _int(ml/min/kg)^3-h	2,560

Total	CLu _int(ml/min/kg)^3-k	50,100

↵3-a Data represent the mean ± calculated S.D.
↵3-b Mean of extrapolated f _u in reaction mixture (cytosol) at 2 and 50 μM (see “Methods”).
↵3-c K _m for C _u.C _u was calculated by f _u × added substrate concentration.
↵3-d K _i for C _u, calculated by equation 3.
↵3-e CLu _int =V _max/K _m.
↵3-f Obtained by multiplying the value (ml/min/mg protein) by 50.7.
↵3-g Obtained by multiplying the value (ml/min/g liver) by 40 (Houston, 1994).
↵3-h Mean value of the four stereoisomers.
3-i Mean of f _u in the reaction mixture (microsome activated with Brij 58) at 2 and 50 μM (see “Methods”).
↵3-j Obtained by multiplying the value (ml/min/mg protein) by 45.4.
↵3-k Sum of mean CLu _int for sulfation and glucuronidation.