1′-OH-MDZ/4-OH-MDZ metabolite concentration ratios from incubations of MDZ with human jejunal microsomes
| Initial MDZ concentration | ||||
|---|---|---|---|---|
| 0.25 | 1.00 | 4.00 | 8.00 | |
| μm | ||||
| CYP3A4 | ||||
| HI-19 | 7.4 | 8.1 | 6.8 | 5.6 |
| HI-20 | 9.0 | 8.9 | 7.1 | 5.8 |
| HI-28 | 8.5 | 8.6 | 7.0 | 5.7 |
| CYP3A4 and CYP3A5 | ||||
| HI-30 | 15.4 | 12.1 | 12.2 | 9.7 |
| HI-31 | 11.2 | 10.6 | 8.7 | 7.0 |
| HI-35 | 11.1 | 10.3 | 8.3 | 6.7 |
Microsomes prepared from the jejunum of each of six subjects were selected based on the results of prescreening for the presence of CYP3A4 only or CYP3A4 and CYP3A5. The microsomes from each of these subjects were incubated with varying concentrations of MDZ. Metabolite formation was quantitated as described in Experimental Procedures. The ratios of 1′-OH-MDZ/4-OH-MDZ for all permutations are presented.