Table 4

The inhibitory effects of gemfibrozil for CYP2C9-mediated tolbutamide hydroxylation in human liver microsomes in the absence and presence of 5 mg/ml Hsa and 0.5 mg/ml Hlc

Incubation	K_i (μM)
Incubation	Total^4-a	Unbound^4-b
Without Hsa and Hlc	6	6
With Hlc	8	8
With Hsa	20 (40)^4-c	4
With Hsa and Hlc	36 (72)^4-c	9

All incubations were performed in duplicate; the mean of duplicate determinations was used for the nonlinear regression analysis to estimate the K_i values (see Experimental Procedures for details).

↵4-a Total K_iof gemfibrozil estimated using the competitive inhibition model:V_i = V_max · S_u/[K_m (1 + I/K_i) + S_u], where S_u is the unbound tolbutamide concentration, and I is the total gemfibrozil concentration.
↵4-b Unbound K_i of gemfibrozil estimated using V_i =V_max · S_u/[K_m(1 + I_u/K_i) + S_u], where S_u is unbound tolbutamide, and I_u is unbound gemfibrozil.
↵4-c Total K_i of gemfibrozil estimated using V_i =V_max · S/[K_m (1 + I/K_i) + S], where S is total tolbutamide, and I is total gemfibrozil.