A comparison of Vmax and Km values determined using MMHHs from this study with those determined in the cryopreserved human hepatocytes and HLMs
The Vmax and Km values and the calculated ratio of the values for MMHH to that for hepatocytes and human liver microsomes are shown. Vmax values are in pmol/min per million cells for MMHH and hepatocytes; Km values are in ยตM.
| P450 Isoforms | Marker Reaction | MMHH | Hepatocytes | HLM | Reference for Hepatocytes | Reference for Human Liver Microsomes | MMHH/Hepatocyte Ratio | MMHH/HLM Ratio | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Vmax | Km | Vmax | Km | Km | Vmax | Km | Vmax | ||||
| CYP1A2 | Phenacetin deethylation | 80 | 11 | NA | NA | 112.7 | NA | Li et al. (2015) | NA | NA | 0.10 |
| CYP2A6 | Coumarin hydroxylation | 112 | 2 | NA | NA | 1.9 | NA | Hosono et al. (2017) | NA | NA | 1.05 |
| CYP2B6 | Bupropion hydroxylation | 136 | 67 | 21 | 41 | 130 | Li and Schlicht (2014) | Faucette et al. (2000) | 6.5 | 1.6 | 0.52 |
| CYP2C8 | Amodiaquine deethylation | 517 | 1 | 334 | 10 | 1 | Li and Schlicht (2014) | Li et al. (2015) | 1.5 | 0.1 | 1.00 |
| CYP2C9 | Diclofenac hydroxylation | 3273 | 2 | 290 | 7 | 22.4 | Brown et al. (2007) | Siu and Lai (2017) | 11.3 | 0.3 | 0.09 |
| CYP2C19 | Mephenytoin hydroxylation | 50 | 45 | 16 | 13 | 56.8 | Brown et al. (2007) | Siu and Lai (2017) | 3.1 | 3.5 | 0.79 |
| CYP2D6 | Dextromethorphan demethylation | 37 | 2 | 50 | 1 | 2.9 | Brown et al. (2007) | Li et al. (2015) | 0.7 | 2.0 | 0.69 |
| CYP2E1 | Chlorzoxazone hydroxylation | 462 | 465 | NA | NA | 149.8 | NA | Li et al. (2015) | NA | NA | 3.10 |
| CYP3A4 | Midazolam hydroxylation | 215 | 4 | 20 | 4 | 8.4 | Li and Schlicht (2014) | Siu and Lai (2017) | 10.8 | 1.0 | 0.48 |
| CYP3A4 | Testosterone hydroxylation | 592 | 70 | 1800 | 24 | 10.2 | Brown et al. (2007) | Siu and Lai (2017) | 0.3 | 2.9 | 6.86 |
NA, not Available.