TABLE 3

Kinetic parameters for oxidation activities of paclitaxel, tolbutamide, flurbiprofen, and omeprazole by recombinant P450 2C enzymes and liver microsomes from marmosets and humans

Drug OxidationEnzyme SourceKmVmaxVmax/Km
μMmin−1μM−1 min−1
Paclitaxel 6α-hydroxylationMarmoset 2C842 ± 101.6 ± 0.20.038 ± 0.010
Human 2C811 ± 379 ± 117.2 ± 2.2
MLM44 ± 80.020 ± 0.0010.00045 ± 0.00009
HLM27 ± 50.22 ± 0.010.0081 ± 0.0016
Tolbutamide methyl hydroxylationMarmoset 2C82210 ± 31398 ± 50.044 ± 0.007
Marmoset 2C19217 ± 2720 ± 10.092 ± 0.012
Human 2C81040 ± 40341 ± 60.039 ± 0.016
Human 2C9284 ± 4555 ± 20.19 ± 0.03
MLM373 ± 1031.0 ± 0.10.0027 ± 0.0008
HLM165 ± 140.79 ± 0.010.0048 ± 0.0004
Flurbiprofen 4-hydroxylationMarmoset 2C8155 ± 301.4 ± 0.10.0090 ± 0.0019
Marmoset 2C19161 ± 5712 ± 20.075 ± 0.029
Marmoset 2C5885 ± 110.80 ± 0.100.0094 ± 0.0017
Human 2C915 ± 427 ± 21.8 ± 0.5
MLM34 ± 50.070 ± 0.0030.0021 ± 0.0003
HLM9.1 ± 0.30.33 ± 0.010.036 ± 0.002
Omeprazole 5-hydroxylationMarmoset 2C1923 ± 1352 ± 82.3 ± 1.3
Human 2C1916 ± 334 ± 22.1 ± 0.4
MLM30 ± 2 (Km1)0.58 ± 0.03 (Vmax1)0.019 ± 0.002 (Vmax1/ Km1)
325 ± 18 (Km2)1.7 ± 0.1 (Vmax2)0.0052 ± 0.0004 (Vmax2/ Km2)
HLM36 ± 3 (Km1)0.33 ± 0.02 (Vmax1)0.0092 ± 0.0009 (Vmax1/ Km1)
727 ± 40 (Km2)1.8 ± 0.1 (Vmax2)0.0025 ± 0.0002 (Vmax2/ Km2)
  • HLM, human liver microsomes; Km1, low Km; Km2, high Km; MLM, marmoset liver microsomes; Vmax1, low Vmax; Vmax2, high Vmax.