TABLE 3

Kinetic characteristics of TRZ 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-TRZ
4-OH-TRZ
1-OH-TRZ
4-OH-TRZ
1-OH-TRZ
4-OH-TRZ
V max a 1.3 ± 0.3 3.3 ± 1.3 0.77 1.7 0.38 0.6
Km (μ M) 104 ± 17 238 ± 21 22 119.7 18 76.9
Vmax/Kmb 15.1 ± 3.4 13.6 ± 4.9 35 14.2 21.1 7.8
Ks (μ M) 5995 ± 1155 3410 8305
IC50 for ketoconazole (μ M)
0.045 ± 0.004
0.043 ± 0.002
0.050
0.049
0.7
0.92

  • ↵ 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 of P450 for rCYP3A4 and rCYP3A5.