TABLE 1

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).