Table 2.

Kinetic Parameters of Sunitinib Metabolite Formation in Single Donor Human Liver Microsomes (HH581 and HH741)^a

kinetic parameter	M1b	M3e	M5
HH581
Km, μM	–	13 ± 3.0	7.5 ± 3.4
Vmaxc	–	0.4 ± 0.04	0.006 ± 0.0008
Vmax/Kmd	23 ± 1.7	0.022 ± 0.008	0.0008 ± 0.0005
HH741
Km, μM	–	–	12 ± 8.8
Vmaxc	–	–	0.003 ± 0.0009
Vmax/Kmd	32 ± 4.2	0.004 ± 0.001	0.0003 ± 0.0003

^aKinetic parameters were estimated using GraphPad Prism software. The results are shown as the means ± SD from three independent experiments (n = 3) performed in triplicate each.

^bFormation of M1 did not saturate at substrate concentrations up to 50 μM; therefore, the K_m and V_max values for M1 were not determined, and the linear slope of the rate vs substrate concentration graph was used to estimate catalytic efficiency of M1 formation (V_max/K_m).

^cV_max for M3 and M5 is shown as the maximum peak area ratio for metabolite to internal standard.

^dV_max/K_m for M1 is in units of μL min⁻¹ μM⁻¹ based on calculation of M1 formation using an authentic standard. V_max/K_m for M3 and M5 is in units of peak area ratio/μM.

^eFormation of M3 did not saturate at substrate concentrations up to 50 μM for HH741; therefore, the linear slopes of the M3 peak area ratio vs substrate concentration graphs were calculated to estimate V_max/K_m for both HH741 and HH581 for comparison.