Kinetic parameters of glucuronidation from incubations with individual HLMs and pooled MLMs (minimal n = 3 animals and triplicate determinations per data point)
| Liver Microsomes | SN-38 | Ezetimibe | Naloxone | |||
|---|---|---|---|---|---|---|
| Km | Vmax | Km | Vmax | Km | Vmax | |
| μM | pmol/min·mg | μM | pmol/min·mg | μM | pmol/min·mg | |
| Human liver microsomes | ||||||
| HH83 (WT) | 0.964 ± 0.274 | 162 ± 10.9 | 5.18 ± 2.28 | 781 ± 85.9 | 58.5 ± 6.85 | 1593 ± 50.1 |
| HH112 (WT) | 0.680 ± 0.217 | 88.2 ± 6.73 | 14.7 ± 4.43 | 1515 ± 146 | 54.6 ± 6.49 | 2059 ± 67.6 |
| HH9 (*28/*28) | 1.46 ± 0.637 | 21.0 ± 2.37 | 16.9 ± 3.62 | 1619 ± 116 | 34.5 ± 6.66 | 1882 ± 91.3 |
| HH81 (*28/*28) | 0.635 ± 0.253 | 17.6 ± 1.51 | 11.5 ± 3.47 | 1330 ± 120 | 63.1 ± 15.7 | 1986 ± 149 |
| Mouse liver microsomes | ||||||
| WT C57BL/6 mouse | 3.59 ± 1.21 | 201 ± 21.5 | 15.0 ± 3.11 | 859 ± 64.5 | 278 ± 23.6 | 1635 ± 55.7 |
| Tg(UGT1A1*28)Ugt1(−/−) | 2.42 ± 1.23 | 43.6 ± 6.36 | 35.6 ± 2.33 | 1093 ± 31.7 | 363 ± 39.3 | 1787 ± 84.1 |
| Tg(UGT1A1*28)Ugt1(−/−) with pb treatment | 1.44 ± 0.359 | 497 ± 28.8 | 20.0 ± 3.31 | 1025 ± 65.8 | 432 ± 31.6 | 1723 ± 58.1 |
WT, C57BL/6 mouse; pb, phenobarbital.