TABLE 3

Effect of avasimibe and prototypical inducers on CYP3A4 and MDR1 mRNA in primary human hepatocytes

Results are expressed as fold increase over control hepatocytes. Primary human hepatocytes (n = 3 wells/treatment) were incubated for 48 h with 0.1% DMSO control or one of the positive controls: rifampin or phenobarbital or negative controls β-NF or 3-MC or avasimibe at 1 or 5 μg/ml. At the end of these treatments, the culture medium was discarded; RNA extracted, reverse transcribed, and fluorescently labeled; and microarray analysis was conducted as described under Materials and Methods. Values represent fold increase over control. Each sample was analyzed in quadruplicate and each value represents the mean ± S.D. of two preparations.


Compound

CYP3A4

MDR1
Rifampin (50 μM) 22.7 ± 5.6 1.7 ± 0.4
β-NF (50 μM) No change 1.5 ± 0.3
3-MC (8 μM) No change No change
Phenobarbital (2 mM) 8.4 ± 0.7 1.4 ± 0.6
Avasimibe (1 μg/ml) 19.8 ± 4.0 2.3 ± 0.3
Avasimibe (5 μg/ml)
5.9 ± 0.9
1.7 ± 0.2