TABLE 1

-Fold increase in CYP3A4 activity, immunoreactive protein, and mRNA levels compared with solvent treatment in primary human hepatocytes treated for 72 h with rifampicin, phenobarbital, tamoxifen, 4OHT, and NDMT Mean ± S.D., n = 3 or 4 donors.

Rifampicina 10 μM
PBa 2 mM
Tamoxifen
4OHT
NDMT
1 μM
5 μM
10 μM
1 μM
5 μM
10 μM
1 μM
5 μM
10 μM
CYP3A4 activityb 10.54* ± 1.89 8.95* ± 2.97 1.30 ± 0.15 2.12* ± 0.77 2.4* ± 0.39 2.05 ± 0.38 7.51* ± 2.61 6.38* ± 1.14 0.8 ± 0.32 0.65 ± 0.21 0.45 ± 0.26
CYP3A4 protein levels 9.43* ± 3.83 7.65* ± 2.8 1.51 ± 0.11 4.03* ± 1.92 4.46* ± 1.64 1.60 ± 0.17 5.79* ± 1.05 7.41* ± 1.69 0.70 ± 0.22 0.88 ± 0.15 0.91 ± 0.31
CYP3A4 mRNA levelsc
13.46* ± 6.77
12.01* ± 5.3
1.5 ± 0.37
3.3* ± 0.37
4.8* ± 1.63
3.3* ± 0.17
5.57* ± 1.03
9.03* ± 3.1
1.2 ± 0.29
0.98 ± 0.35
1.81 ± 0.61

  • PB, phenobarbital

  • ↵* Significant difference at p < 0.05 by t test

  • ↵ a Prototypical inducers used as positive controls

  • ↵ b Measured as the rate of testosterone 6β-hydroxylation

  • ↵ c Measured by Northern blot analysis, normalized to 18s RNA