TABLE 1

CYP2B6 induction in primary human hepatocytes

Human hepatocytes from five donors cultured in six-well Biocoat plates were treated for 24 h with DMSO (0.1%), 10 μM RIF, 1 μM CITCO, and the indicated concentrations of CMZ, EFV, and NVP. Total RNA was extracted from one to two wells per treatment, reverse-transcribed, and subjected to TaqMan real-time PCR. CYP2B6 mRNA levels were normalized to those of β-actin. Fold induction data relative to vehicle control represent the mean of triplicate PCR determinations.


Drug

Hu177

Hu190

Hu214

HCS009

HCS014
CMZ
    1 NA 1.6 1.3 2.0 1.4
    10 6.0 4.3 4.6 4.9 2.9
    25/50a 10.5 8.6 4.9 6.5 4.1
EFV
    1 4.4 3.4 2.1 4.2 1.9
    5/10b 7.9 7.9 2.8 6.2 2.6
    10/25b 5.5 7.4 3.3 5.8 3.7
NVP
    1 1.4 1.6 1.3 1.6 1.0
    10 3.4 4.1 3.9 4.5 1.8
    50 6.2 12.0 8.2 9.8 3.7
RIF
    10 NA 9.7 10.8 4.5 3.2
CITCO
    1
13.0
25.8
NA
10.8
5.3
  • NA, data not available.

  • a Highest tested concentration of CMZ was 25 μM in HCS009 and HCS014 and 50 μM in the remaining livers.

  • b Hepatocytes from donor HCS009 and HCS014 were treated with 1, 5, and 10 μM EFV, whereas those from other donors were treated with 1, 10, and 25 μM.