Figure 3.
Induction effects of NVP and its analogs on CYP3A4 gene expression and activity in primary human hepatocytes. Fold change of CYP3A4 mRNA (A) and midazolam 1′-hydroxylation activity (B) in pooled primary human hepatocytes dosed for 72 h with 25 μM and 100 μM NVP, 2-nitro-NVP, 12-d3-NVP, or 3-bromo-NVP. DMSO and rifampicin (10 μM) treatments were used for solvent control and positive control for induction, respectively. Bars represent the means of at least four biological replicates ± standard deviations. Data were analyzed by one-way ANOVA against the DMSO control. Statistical differences are shown by **, ***, and **** corresponding to the following significance levels: p < 0.01, p < 0.001, and p < 0.0001, respectively. ns, not significant; NVP, nevirapine; RIF, rifampicin.