Effect of CYP3A5 Expression on the Inhibition of CYP3A-Catalyzed Drug Metabolism: Impact on Modeling CYP3A-Mediated Drug-Drug Interactions

Supplemental Data

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    Supplemental information

    Supplemental Table 1 - Summary of Curve Fitting and IC50 Determination for KTZ with rCYP3A4 and rCYP3A5

    Supplemental Table 2 - Summary of Curve Fitting and IC50 Determination for ITZ with rCYP3A4 and rCYP3A5

    Supplemental Table 3 - ITZ as an Inhibitor of Fully Reconstituted Wild-Type and Mutant CYP3A4

    Supplement Figure S1 - Representative IC50 plots describing the inhibition of rCYP3A4- and rCYP3A5-catalyzed metabolism of MDZ, TST, terfenadine and vincristine by ITZ (S/Km ratio ~1.0)

    Supplement Figure S2 Representative IC50 plots describing the inhibition of rCYP3A4- and rCYP3A5-catalyzed metabolism of MDZ, TST, terfenadine and vincristine by KTZ (S/Km ratio ~1.0)

    Supplement Figure S3 - Representative IC50 plots describing the inhibition of rCYP3A4- and rCYP3A5-catalyzed metabolism of MDZ, TST, terfenadine and vincristine by ITZ (S/Km ratio ~0.05)

    Supplement Figure S4 - Representative IC50 plots describing the inhibition of rCYP3A4- and rCYP3A5-catalyzed metabolism of MDZ, TST, terfenadine and vincristine by KTZ (S/Km ratio ~0.05)

    Supplement Figure S5 - Representative Type II ligand spectral titration plot for ITZ with rCYP3A4 (A) and rCYP3A5 (B) and KTZ with rCYP3A4 (C) and rCYP3A5 (D)

    Supplement Figure S6 - Representative IC50 plots describing the inhibition wild-type and mutant CYP3A4-catalyzed TST (25 and 100 muM) metabolism by ITZ

    Supplement Figure S7 - Representative IC50 plots describing the inhibitory effect of KTZ and ITZ on CYP3A-catalyzed metabolism of MDZ in HLM

    Supplement Figure S8 - Representative IC50 plots describing the inhibitory effect of KTZ and ITZ on CYP3A-catalyzed metabolism of TST in HLM