Kinetic parameters for midazolam metabolism by liver and intestinal microsomes
All values are the means of three independent experiments ± S.D. Incubations were performed as described under Materials and Methods.
Microsomes and Strains | 1′-OH Midazolam | 4-OH Midazolam | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
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 | ||||||||||
Cyp3a +/+ | 0.95 ± 0.18 | 630 ± 29 | 662 | 8.43 ± 0.27 | 224 ± 12.7 | 26.6 | ||||
Cyp3a −/− | 6.38 ± 1.2 | 735 ± 11 | 115 | 17.5 ± 6.9 | 49.8 ± 5.0 | 2.36 | ||||
Human | 2.93 ± 0.33 | 2097 ± 155 | 715 | 38.7 ± 6.3 | 1226 ± 87 | 27.8 | ||||
Intestine | ||||||||||
Cyp3a +/+ | 10.4 ± 1.8 | 62.3 ± 3.2 | 6.02 | 55.9 ± 2.0 | 38.0 ± 5.2 | 0.68 | ||||
Cyp3a −/− | — | — | — | — | — | — | ||||
Human | 1.61 ± 0.04 | 596 ± 18 | 369 | 24.5 ± 3.3 | 330 ± 11 | 13.5 |
—, no metabolite detected (detection limit <5 pmol/min/mg protein).