TABLE 2 

In vitro mRNA induction parameters, EC50 and Emax, can differentiate commonly regulated genes

The EC50 and Emax values were determined for each gene regulated by PXR and CAR or PXR, CAR, and AhR for each donor. Dose-response curves were generated for mRNA expression (fold induction normalized to 0.1% DMSO) vs. the concentration-response for selective activators rifampin (0.1–10 µM), CITCO (0.01–1 µM) and omeprazole (0.03–3 µM), and individual fitting was carried out. Emax (relative fold induction of mRNA), EC50 (µM), S.E.

GeneRifampinCITCOOmeprazole
BNAFOSHH1089BNAFOSHH1089BNAFOSHH1089
CYP1A1Emax ± S.E.2.40 ± 0.393.08 ± 0.450.81 ± 0.10a1.83 ± 0.131.66 ± 0.18a2.37 ± 0.5370.3 ± 9.10a43.2 ± 7.5036.9 ± 16.7
EC50 ± S.E.0.51 ± 0.550.75 ± 0.60NA0.01 ± 0.005NA0.28 ± 0.29NA2.13 ± 0.536.39 ± 4.15
CYP3A4Emax ± S.E.100 ± 7.5478.1 ± 5.6035.2 ± 2.885.31 ± 0.445.37 ± 0.463.75 ± 0.312.25 ± 0.372.64 ± 0.481.67 ± 0.10a
EC50 ± S.E.0.21 ± 0.080.13 ± 0.050.2 ± 0.080.18 ± 0.050.17 ± 0.060.07 ± 0.030.74 ± 0.620.82 ± 0.67NA
UGT1A1Emax ± S.E.4.87 ± 0.345.05 ± 0.323.24 ± 0.282.83 ± 0.222.12 ± 0.113.31 ± 0.262.08 ± 0.16a3.68 ± 1.202.56 ± 0.31
EC50 ± S.E.0.57 ± 0.190.26 ± 0.090.18 ± 0.110.08 ± 0.040.07 ± 0.020.04 ± 0.02NA3.12 ± 2.410.65 ± 0.37
CYP2B6Emax ± S.E.26.5 ± 2.3319.8 ± 2.987.29 ± 0.8433.3 ± 3.0617.2 ± 0.6813.1 ± 0.62
EC50 ± S.E.0.42 ± 0.160.41 ± 0.270.33 ± 0.190.08 ± 0.030.03 ± 0.0060.04 ± 0.008
CYP2C8Emax ± S.E.4.47 ± 0.4311.0 ± 2.0013.7 ± 3.395.31 ± 0.392.13 ± 0.083.16 ± 0.17
EC50 ± S.E.0.07 ± 0.060.15 ± 0.150.20 ± 0.240.04 ± 0.010.03 ± 0.010.02 ± 0.007
UGT1A4Emax ± S.E.5.56 ± 0.2610.3 ± 0.976.07 ± 0.612.01 ± 0.191.72 ± 0.102.57 ± 0.16
EC50 ± S.E.0.67 ± 0.140.38 ± 0.170.25 ± 0.140.10 ± 0.060.12 ± 0.050.07 ± 0.03
  • a NA, not applicable in the absence of Emax.

  • MOI is reported where Emax was not reached.