TABLE 4

Kinetic parameters for glimepiride hydroxylation activities of wild-type and variant CYP2C9s

Data are presented as the mean ± S.D. of three to four different expression experiments.

Recombinant Enzymes (Amino Acid Alteration)
Km
Vmax
Clearance (Vmax/Km)
μM pmol/min/pmol P450 μl/min/pmol P450
CYP2C9.1 (wild type) 0.18 ± 0.03 1.65 ± 0.11 9.22 ± 1.85
CYP2C9.3 (I359L) 0.13 ± 0.03 0.22 ± 0.06*** 1.86 ± 0.94***
CYP2C9.13 (L90P) 1.29 ± 0.37*** 0.16 ± 0.03*** 0.13 ± 0.03***
CYP2C9.26 (T130R) 0.16 ± 0.05 0.14 ± 0.03*** 0.94 ± 0.42***
CYP2C9.28 (Q214L) 0.25 ± 0.04 0.98 ± 0.11*** 4.04 ± 0.91***
CYP2C9.30 (A477T) 0.14 ± 0.03 0.28 ± 0.04*** 2.32 ± 0.10***
CYP2C9.33 (R132Q) 0.20 ± 0.04 0.013 ± 0.001*** 0.07 ± 0.01***
CYP2C9.34 (R335Q) 0.16 ± 0.03 1.05 ± 0.09*** 6.62 ± 0.55**
Gentest CYP2C9.1 0.14 0.88 6.40
Gentest human liver microsome
0.56
0.10
0.19

  • ↵** P < 0.01 vs. wild type. One-way ANOVA with a post hoc Dunnett multiple comparisons test.

  • ↵*** P < 0.001 vs. wild type.