TABLE 1

Kinetic parameters for probe compound metabolism in 8HUM mice

Hepatic microsomal fractions from pooled rifampicin-treated male and female 8HUM mice or pooled human liver microsomes were used. Data presented as mean ± S.D. on biologic triplicate samples. F-test comparing 8HUM and HLM data for each substrate showed no significant difference. Enzyme activities were determined as described in Materials and Methods.

SubstrateCYP1A2 7-EthoxyresorufinCYP2C9 TolbutamideCYP2D6 DebrisoquineCYP3A4 Midazolam
HLM8HUMHLM8HUMHLM8HUMHLM8HUM
Km (μM)0.22 ± 0.040.35 ± 0.0573 ± 16137 ± 3625 ± 757 ± 80.73 ± 0.201.2 ± 0.3
Vmax (pmol/min per milligram protein)12.3 ± 0.520.7 ± 0.92.5 ± 0.12.7 ± 0.225 ± 298 ± 61500 ± 1005100 ± 500