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

IncubationKi (μM)
Without Hsa and Hlc66
With Hlc88
With Hsa20 (40)4-c 4
With Hsa and Hlc36 (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 Ki values (see Experimental Procedures for details).

  • 4-a  Total Kiof gemfibrozil estimated using the competitive inhibition model:Vi = Vmax · Su/[Km (1 + I/Ki) + Su], where Su is the unbound tolbutamide concentration, and I is the total gemfibrozil concentration.

  • 4-b  Unbound Ki of gemfibrozil estimated using Vi =Vmax · Su/[Km(1 + Iu/Ki) + Su], where Su is unbound tolbutamide, and Iu is unbound gemfibrozil.

  • 4-c  Total Ki of gemfibrozil estimated using Vi =Vmax · S/[Km (1 + I/Ki) + S], where S is total tolbutamide, and I is total gemfibrozil.