Table 3

Enzyme kinetic parameters of sulfation and glucuronidation for four stereoisomers of troglitazone with ddY mouse liver

ConjugationParameter   Stereoisomer4-a
SSSRRSRR
Sulfation f u 4-b 0.05800.0631 
V max (nmol/min/mg protein)0.0456  ± 0.00450.243  ± 0.0460.0170  ± 0.00110.0201  ± 0.0053
K m (μM)4-c 0.412  ± 0.0591.56  ± 0.360.335  ± 0.0340.643  ± 0.238
CLu int (mol/min/mg protein)4-d 0.111  ± 0.0190.156  ± 0.0460.0507  ± 0.00610.0313  ± 0.0142
V max(nmol/min/g liver)4-e 2.4312.90.9041.07
CLu int (ml/min/g liver)4-e 5.918.302.701.67
CLu int(ml/min/kg)4-f 23633210866.6
MeanCLu int(ml/min/kg)4-g 186
Glucuronidation f u 4-h 0.01020.00971
V max (nmol/min/mg protein)2.74  ± 0.532.65  ± 1.006.10  ± 2.990.994  ± 0.021
K m (μM)4-c 1.16  ± 0.242.58  ± 1.011.71  ± 0.890.101  ± 0.003
CLu int (ml/min/mg protein)4-d 2.36  ± 0.671.03  ± 0.563.57  ± 2.549.84  ± 0.36
V max (nmol/min/g liver)4-i 11210824940.6
CLu int (ml/min/g liver)4-i 96.342.0146400
CLu int(ml/min/kg)4-f 3,8501,6805,83016,100
MeanCLu int(ml/min/kg)4-g 6,870
Total CLu int(ml/min/kg)4-j 7,050
  • 4-a Data represent the mean ± calculated S.D.

  • 4-b Mean of extrapolated f u in the reaction mixture (cytosol) at 2 and 50 μM (see “Methods”).

  • 4-c K m for C u.C u was calculated by f u × added substrate concentration.

  • 4-d CLu int =V max/K m.

  • 4-e Obtained by multiplying the value (ml/min/g liver) by 53.2.

  • 4-f Obtained by multiplying the value (ml/min/g liver) by 40 (Houston, 1994).

  • 4-g Mean value of the four stereoisomers.

  • 4-h Mean of f u in the reaction mixture (microsome activated with Brij 58) at 2 and 50 μM (see “Methods”).

  • 4-i Obtained by multiplying the value (ml/min/mg protein) by 40.8.

  • 4-j Sum of mean CLu int for sulfation and glucuronidation.