TABLE 3

Kinetic parameters for losartan oxidation 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/nmol P450 μl/min/nmol P450
CYP2C9.1 (wild type) 1.12 ± 0.13 780 ± 82 704 ± 77
CYP2C9.3 (I359L) 0.99 ± 0.10 157 ± 30*** 161 ± 42***
CYP2C9.13 (L90P) 2.76 ± 0.64*** 47.0 ± 2.3*** 17.6 ± 3.6***
CYP2C9.26 (T130R) 1.50 ± 0.13 40.3 ± 6.2*** 26.8 ± 2.0***
CYP2C9.28 (Q214L) 2.03 ± 0.42*** 180 ± 18*** 90.2 ± 11.7***
CYP2C9.30 (A477T) 0.77 ± 0.12 4.7 ± 0.4*** 6.3 ± 1.3***
CYP2C9.33 (R132Q) 1.03 ± 0.21 7.3 ± 0.3*** 7.3 ± 1.4***
CYP2C9.34 (R335Q) 1.06 ± 0.11 550 ± 27*** 526 ± 75***
BD Gentest CYP2C9.1 1.34 630 470
BD Gentest human liver microsome
2.85
48.2
16.9
  • *** P < 0.001 vs. wild type. One-way ANOVA with a post hoc Dunnett multiple comparisons test.