Metabolic Activity | |||
---|---|---|---|
1′-OH Midazolam | 4-OH Midazolam | ||
pmol/min per milligram of protein | |||
Liver microsomes | Cyp3a KO/uPA/SCID mice | 281.5 ± 21.1 | 63.9 ± 14.0 |
Cyp3a KO chimeric mice | 846.2 ± 372.3* | 420.9 ± 194.8* | |
PXB-mice | 611.7 ± 32.0 | 306.1 ± 6.5 | |
Intestinal microsomes | Cyp3a KO/uPA/SCID mice | 0.6 ± 0.4 | 0.7 ± 0.1 |
Cyp3a KO chimeric mice | 1.3 ± 0.7 | 0.9 ± 0.0 | |
PXB-mice | 14.9 ± 15.5 | 9.8 ± 9.5 |
* P < 0.05 versus Cyp3a KO/uPA/SCID mice.
Midazolam 1′- and 4-hydroxylation in liver and intestinal microsomes were determined using LC-MS/MS. Midazolam (50 μM) was incubated in liver (0.1 mg/ml) and intestinal (0.5 mg/ml) microsomes at 37°C for 5 minutes. Data are shown as mean ± S.D. obtained from three male mice. Statistical differences in three mice groups were determined using one-way analysis of variance followed by Tukey’s test.