TABLE 2

Kinetic characteristics of MDZ biotransformation in vitro by HLMs, rCYP3A4, and rCYP3A5, and IC50 values for ketoconazole

Results are expressed as mean ± S.E.

HLMs (n = 6)
rCYP3A4
rCYP3A5
1-OH-MDZ
4-OH-MDZ
1-OH-MDZ
4-OH-MDZ
1-OH- MDZ
4-OH-MDZ
V max a 0.18 ± 0.03 0.42 ± 0.05 0.32 1.2 0.37 0.37
Km (μM) 3.9 ± 0.9 77.5 ± 9.5 0.8 68.6 2.3 33.4
Vmax/Kmb 69 ± 20 6.1 ± 1.2 400 17.3 161 11.1
IC50 for ketoconazole (μM)
0.097 ± 0.03
0.089 ± 0.04
0.044
0.053
0.56
0.73

  • ↵ a Units are nmol/min/mg protein for HLMs and nmol/min/pmol P450 for rCYP3A4 and rCYP3A5.

  • ↵ b For clearance (Vmax/Km ratio), units are μl/min/mg protein for HLMs and μl/min/pmol P450 for rCYP3A4 and rCYP3A5.