TABLE 2

Kinetic parameters obtained for each compound in microsomes and hepatocytes


P450

Substrate

KM,u (or S50,u)

Vmax

CLint,u
Cryopreserved Human Hepatocytes
Human Liver Microsomes
Cryopreserved Human Hepatocytes
Human Liver Microsomes
Cryopreserved Human Hepatocytes
Human Liver Microsomes
μM nmol/min/106 cells or mg protein μl/min/106 cells or mg protein
CYP2C9 Tolbutamide methylhydroxylation 112 ± 38 212 ± 90 0.015 ± 0.002 0.37 ± 0.08 0.06 ± 0.03 1.9 ± 0.4
Diclofenac 4′-hydroxylation 7.4 ± 0.7 3.7 ± 0.4 0.29 ± 0.20 1.8 ± 0.3 38 ± 23 501 ± 28
S-Warfarin 7-hydroxylation 2.7 ± 1.5 4.3 ± 0.02 0.001 ± 0.001 0.004 ± 0.001 1.0 ± 1.0 0.87 ± 0.22
CYP2C19 S-Mephenytoin 4′-hydroxylation 13 ± 4 30.3 0.016 ± 0.004 0.04 1.4 ± 0.7 1.37
CYP3A4 Quinidine (3S)-3-hydroxylation 50 ± 8 78 0.31 ± 0.33 0.88 7.0 ± 7.9 11
Nifedipine oxidation 16 ± 12 11 1.07 ± 1.15 0.95 56 ± 26 87
Testosterone 6β-hydroxylation 24 ± 1a 47a 1.8 ± 1.3 6.1 31 ± 22 131
Terfenadine methylhydroxylation 0.49 ± 1.73 1.0 ± 0.5 91 ± 57 43 ± 14 1410 ± 590 11,100 ± 275
Terfenadine N-dealkylation 1.7 ± 1.2 0.8 ± 0.02 21 ± 8 2.8 ± 0.4 154 ± 102 90 ± 13
Dextromethorphan N-demethylationb 139 ± 88 221 ± 50 0.28 ± 0.24 0.61 ± 0.1 2.8 ± 2.5 2.8 ± 0.3
CYP2D6 Bufuralol 1-hydroxylation 2.1 ± 1c 2.8c 0.028 ± 0.016c 0.071c 17 ± 15c 26c
44 ± 39d 43.3d 0.027 ± 0.002d 0.076d 0.98 ± 0.65d 1.8d
Dextromethorphan O-demethylatione 0.9 ± 0.3c 2 ± 0.4c 0.05 ± 0.03c 0.134 ± 0.01c 63 ± 46c 69 ± 16c


44 ± 15d
106 ± 55d
0.06 ± 0.017d
0.16 ± 0.03d
1.6 ± 0.90d
1.72 ± 0.5d
  • a Denotes S50 value.

  • b Represents 3-methoxymorphinan.

  • c Represents the high-affinity, low-capacity pathway.

  • d Represents the low-affinity, high-capacity pathway.

  • e Represents dextrorphan.