TABLE 3

Michaelis-Menten kinetics for different selective P450 marker reactions


P450

Substrate

Human Liver Microsomes

P450-Expressing Cells

Human Hepatocytes
Km
Vmaxa
Km
Vmax
Km
Vmax
1A2 Methoxyresorufin 0.95 ± 0.21b 32.2 ± 7.8 5.8 ± 2.8 64.3 ± 15.7 1.1 12.7
2A6 Coumarin 5.6 ± 2.9 646 ± 157 9.1 ± 1.3 349 ± 75 2.6 86.6
2B6 Benzoxyresorufin 4.8 ± 1.5 13.3 ± 4.6 7.2 ± 1.3 5.4 ± 2.4 6.1 6.9
2C8 Paclitaxel 13.3 ± 8.3 109.1 ± 34.9 16.3 ± 1.2 81.0 ± 17.4 N.D. N.D.
2C9 Diclofenac 19.7 ± 9.6 2865 ± 492 99.0 ± 5.4 2066 ± 17 85.3 73.4
2C19 Mephenytoin 19.5 ± 5.6 392 ± 3.7 30.3 ± 3.3 47.2 ± 15.7 17.0 10.6
2D6 Dextromethorphan 6.0 ± 1.5 401 ± 74 5.2 ± 0.3 77.0 ± 9.9 131.6 142
2E1 Chlorzoxazone 45.6 ± 4.7 1315 ± 162 65.1 ± 13 56.3 ± 17.8 93.0 320
3A4
Testosterone
91.3 ± 35.5
1424 ± 441
34.9 ± 8.7
242 ± 58
31.9
91.0
  • N.D., not determined.

  • a Vmax values are expressed as pmol of metabolite formed per minute and per mg of microsomal protein for assays in human liver microsomes or per mg of total cell protein for assays in intact cells (P450-expressing cells and human hepatocytes)

  • b Data are mean ± S.D. of three independent experiments for human liver microsomes and P450-expressing cell assays or the mean of two experiments for human hepatocyte assays