Kinetic parameters for triazolam metabolism with or without gefitinib (12.5 μM) by CYP3A4-Tg mouse liver and intestinal microsomes
All the values are the means of three independent experiments ± S.D. Incubations were performed as described under Materials and Methods.
| Microsomes | Strain | 1′-OH Triazolam | 4-OH Triazolam | ||||
|---|---|---|---|---|---|---|---|
| Km | Vmax | Vmax/Km | Km | Vmax | Vmax/Km | ||
| μM | pmol/min/mg protein | μl/min/mg protein | μM | pmol/min/mg protein | μl/min/mg protein | ||
| Liver | |||||||
| Control | Cyp3a(−/−)Tg-3A4Hep | 77.2 ± 3.75 | 1320 ± 34.4 | 17.1 | 343 ± 33.8 | 3366 ± 243 | 9.81 |
| Gefitinib | Cyp3a(−/−)Tg-3A4Hep | 22.5 ± 1.46 | 2602 ± 60.2 | 115 | 502 ± 34.1 | 1677 ± 38.1 | 3.34 |
| Intestine | |||||||
| Control | Cyp3a(−/−)Tg-3A4Int | 22.5 ± 1.72 | 349 ± 6.18 | 15.5 | 277 ± 80.9 | 1089 ± 207 | 3.93 |
| Gefitinib | Cyp3a(−/−)Tg-3A4Int | 8.23 ± 0.74 | 812 ± 12.0 | 98.6 | 1329 ± 131 | 1265 ± 97.0 | 0.95 |