TABLE 1

CYP3A4 mRNA change relative to dimethylsulfoxide (DMSO) (0.1%) treatment in hepatocytes from three human donors following incubation with ASV, DCV, BCV, or BCV-M1

DrugTreatmentCYP3A4 mRNAa
Donor 1Donor 2Donor 3
ASVDonorHC3-15HC1-18HC5-10
DMSO (0.1%)111
0.049 µg/ml3.73bND0.802
0.15 µg/ml1.531.861.13
0.49 µg/ml4.723.581.77
1 µg/ml7.795.52.92
2 µg/ml8.6ND3.66
4.9 µg/ml12.16.74.3
10 µg/ml8.7c4.73c3.7
20 µg/ml4.95c2.39c1.74c
Rifampin (10 µM)2618.18.15
DCVDonorHC3-15HC1-18HC5-10
DMSO (0.1%)111
0.16 µg/ml1.381.451.21
0.32 µg/ml1.441.661.34
0.75 µg/ml2.52.271.47
1.6 µg/ml5.595.74.91
2.5 µg/ml7.489.223.7
4 µg/ml12.812.16.35
6 µg/ml20.313.26.68
9.6 µg/ml27.3138.76
Rifampin (10 µM)2618.18.15
BCVDonorHC3-15HC3-17HC5-10
DMSO (0.1%)1.001.001.00
0.15 µg/ml1.961.451.90
0.35 µg/ml3.271.991.67
0.8 µg/ml5.642.592.67
1.5 µg/ml6.362.612.43
3.5 µg/ml5.772.182.64
8 µg/ml3.88c2.092.45
15 µg/ml2.70c1.38c1.43c
30 µg/ml0.29c0.08c0.26c
Rifampin (10 µM)29.803.707.93
BCV-M1DonorHC3-15HC3-17HC5-10
DMSO (0.1%)1.001.001.00
0.028 µg/ml1.041.150.97
0.08 µg/ml1.631.261.05
0.28 µg/ml3.571.991.61
0.8 µg/ml7.172.492.22
2.8 µg/ml8.232.262.41
8 µg/ml5.24c2.141.89c
15 µg/ml3.78c1.87c3.08
30 µg/ml0.32c0.15c0.14c
Rifampin (10 µM)29.803.707.93
  • ND, not determined due to sample analysis error.

  • a Values are relative to vehicle control, normalized to glyceraldehyde 3-phosphate dehydrogenase and are the average of triplicate determinations.

  • b Anomalous data, possibly due to sample analysis error. Data were excluded from the curve fitting.

  • c Data were excluded from the curve fitting because fold increase was <80% of the observed Emaxvalue.