Effect of various chemical inhibitors on MDZ metabolite formation in mouse and human liver microsomes
| Inhibitor | Mouse Microsomes | Human Microsomes | ||
|---|---|---|---|---|
| α-OH-MDZ | 4-OH-MDZ | α-OH-MDZ | 4-OH-MDZ | |
| Percentage of control velocity | ||||
| Troleandomycin2-a 500 μM | 66.0 | 46.5 | 10.2 | 13.0 |
| Ketoconazole 2.5 μM | 58.3 | 9.4 | 8.7 | 6.3 |
| α-Naphthoflavone 5 μm | 95.7 | 103.8 | 124.8 | 97.9 |
| 8-Methoxypsoralen2-a2.5 μM | 74.9 | 97.6 | 94.1 | 95.6 |
| Orphenadrine 200 μM | 67.5 | 85.1 | 78.7 | 89.8 |
| Sulfaphenazole 20 μM | 100.8 | 99.6 | 95.8 | 98.8 |
| Omeprazole 10 μM | 102.0 | 103.1 | 94.9 | 97.6 |
| Quinine 5 μM | 101.9 | 102.7 | 99.6 | 101.8 |
| Quinidine 5 μM | 103.6 | 99.9 | 92.2 | 95.1 |
| DDC2-a | ||||
| 20 μM | 83.1 | 100.4 | 88.2 | 91.7 |
| 100 μM | 15.1 | 0 | 15.5 | 16.8 |
| Chloramphenicol 100 μM | 74.8 | 72.7 | 68.3 | 81.6 |
Experiments were performed with a fixed concentration of MDZ (50 μM) using pooled mouse and human liver microsomes. Each value represents the mean of duplicate incubations. In no case did the duplicates differ by greater than 10%.
↵2-a Mechanism-based inhibitors that were preincubated with microsomes and cofactor before addition of MDZ; all other inhibitors were coincubated with MDZ.