Table 2

Effect of various chemical inhibitors on MDZ metabolite formation in mouse and human liver microsomes

InhibitorMouse MicrosomesHuman Microsomes
Percentage of control velocity
Troleandomycin2-a 500 μM66.046.510.213.0
Ketoconazole 2.5 μM58.
α-Naphthoflavone 5 μm95.7103.8124.897.9
8-Methoxypsoralen2-a2.5 μM74.997.694.195.6
Orphenadrine 200 μM67.585.178.789.8
Sulfaphenazole 20 μM100.899.695.898.8
Omeprazole 10 μM102.0103.194.997.6
Quinine 5 μM101.9102.799.6101.8
Quinidine 5 μM103.699.992.295.1
 20 μM83.1100.488.291.7
 100 μM15.1015.516.8
Chloramphenicol 100 μM74.872.768.381.6

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.