TABLE 1

Kinetic parameters for carvedilol glucuronidation in microsomes from human liver and insect cells expressing human UGTs Each value represents the mean ± S.D. of three independent experiments carried out under the experimental conditions described under Materials and Methods. G1 and G2 formation catalyzed by UGT1A1 and UGT2B7, respectively, was below the lower limit of determination (0.33 pmol/min/mg protein) at all substrate concentrations.


Microsomes

G1

G2
Km
Vmax
Vmax/Km
Km
Vmax
Vmax/Km
μM pmol/min/mg protein μl/min/mg protein μM pmol/min/mg protein μl/min/mg protein
Pooled HLM 26.6 ± 1.6 106 ± 1 3.98 ± 0.23 46.0 ± 4.8 44.5 ± 3.4 0.97 ± 0.03
UGT1A1 <0.33 55.1 ± 6.6 3.63 ± 0.31 0.07 ± 0.01
UGT2B4 22.1 ± 0.8 7.24 ± 0.15 0.33 ± 0.01 28.8 ± 3.3 3.33 ± 0.25 0.12 ± 0.01
UGT2B7
27.9 ± 0.6
7.88 ± 0.15
0.28 ± 0.01

<0.33