Kinetic parameters of diazepam metabolism in liver microsomes from four rat strains
The concentration range of substrate (diazepam) was 0.4 to 40 μM. Other experimental details are described under Materials and Methods. Data are expressed as mean ± S.E.M.
Pathway | Km | Vmax | CLint | Total CLint | ||
|---|---|---|---|---|---|---|
| μM | nmol/min/mg protein | μl/min/mg protein | ||||
| SD | p-Hydroxylation | 5.5 ± 0.5** | 0.5 ± 0.0** | 87.0 ± 2.1** | ||
| 3-Hydroxylation | 71.2 ± 11 | 3.2 ± 0.3 | 48.9 ± 9.0 | 145 ± 11** | ||
| N-Desmethylation | 75.9 ± 9.4 | 0.7 ± 0.1 | 9.5 ± 0.3 | |||
| BN | p-Hydroxylation | 4.3 ± 0.2** | 0.4 ± 0.0** | 86.9 ± 6.5** | ||
| 3-Hydroxylation | 55.9 ± 1.3 | 2.2 ± 0.1 | 38.8 ± 2.9 | 137 ± 10** | ||
| N-Desmethylation | 46.9 ± 1.6 | 0.5 ± 0.0 | 11.2 ± 0.7 | |||
| DA | p-Hydroxylation | 26.7 ± 4.6 | 0.004 ± 0.0 | 0.2 ± 0.0 | ||
| 3-Hydroxylation | 35.7 ± 6.8 | 5.3 ± 0.5** | 163 ± 15** | 185 ± 15** | ||
| N-Desmethylation | 67.5 ± 2.7 | 1.5 ± 0.1** | 22.4 ± 0.6** | |||
| W | p-Hydroxylation | 23.3 ± 1.6 | 0.004 ± 0.0 | 0.2 ± 0.0 | ||
| 3-Hydroxylation | 58.3 ± 6.3 | 2.6 ± 0.2 | 47.9 ± 7.0 | 56 ± 8 | ||
| N-Desmethylation | 87.6 ± 6.6 | 0.7 ± 0.1 | 8.1 ± 0.5 | |||
| EM Wa | p-Hydroxylation | 6.3 ± 0.6** | 0.3 ± 0.1** | 46.0 ± 8.4** | ||
| 3-Hydroxylation | 64.6 ± 15 | 2.8 ± 0.0 | 50.3 ± 15 | 106 ± 24** | ||
|
| N-Desmethylation | 86.1 ± 14 | 0.9 ± 0.1 | 10.4 ± 0.9 |
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