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 |