TABLE 2

Simulated δAUC for CYP2C9 mediated drug-drug interactions

K_i values were determined as described under Materials and Methods using rCYP2C9 and diclofenac as substrate. [I]_{in, total} values and observed δAUC for amiodarone, benzbromarone, fluconazole (both clinical studies), fluvastatin, ketoconazole, miconazole, sertraline, sulfamethiazole, sulfaphenazole, and sulfinpyrazone were retrieved directly from Ito et al. (2004). [I]_{in, total} values and observed δAUC for diclofenac, ibuprofen, and tolbutamide were retrieved from Andersson et al. (2004). [I]_{max, total} values and observed δAUC for zafirlukast were retrieved from Blanchard et al. (2004). [I]_unbound values were calculated by multiplying the [I]_total by the fu_p determined in this laboratory. [I] and K_i values together with the estimated fm_CYP2C9 for the respective in vivo substrates were used in eq. 1 to simulate the δAUC.