EC50 and Emax values for induction of CYP3A4 and CYP2B6 mRNA for compounds tested in Fa2N-4 cells and human hepatocytes
EC50 and Emax are expressed as mean ± calculated S.E. using SigmaPlot version 10 as described under Materials and Methods. Studies conducted with Fa2N-4 cells represent the mean of three independent experiments performed in triplicate. Studies conducted in human hepatocytes (DMQ) represent the mean of one experiment done in duplicate.
Compound | Fa2N-4 | Human Hepatocytes (DMQ) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CYP3A4 | CYP2B6 | CYP3A4 | CYP2B6 | |||||||||||
| EC50 | Emax | EC50 | Emax | EC50 | Emax | EC50 | Emax | |||||||
| μM | fold | μM | fold | μM | fold | μM | fold | |||||||
| Artemisinina | NQ | NQ | NQ | NQ | 21.4 ± 1.8 | 29.4 ± 1.7 | 40.6 ± 28.1 | 12.4 ± 4.0 | ||||||
| CITCOa | NQ | NQ | NQ | NQ | 0.8 ± 0.7 | 5.3 ± 4.9 | 0.01 ± 0.004 | 6.8 ± 0.6 | ||||||
| Phenytoinb | 10.0 ± 1.2 | 9.2 ± 0.8 | NQ | NQ | 5.1 ± 3.1 | 16.9 ± 0.2 | 9.8 ± 2.0 | 10.7 ± 1.5 | ||||||
| Phenobarbitalb,c | NQ | NQ | 204.4 ± 54.4 | 4.99 ± 3.6 | NQ | NQ | 60.4 ± 4.9 | 31.3 ± 1.4 | ||||||
| Rifampicind | 8.0 ± 5.9 | 59.5 ± 17.3 | 8.0 ± 1.6 | 4.1 ± 0.5 | 0.4 ± 0.3 | 52.5 ± 26.7 | 2.3 ± 0.5 | 12.9 ± 0.8 | ||||||
| Moricizinee | 1.6 ± 0.5 | 7.1 ± 0.5 | NQ | NQ | 1.3 ± 0.2 | 17.2 ± 0.8 | 0.05f | 2.8 ± 0.4 | ||||||
| Bosentand | 1.8 ± 0.7 | 11.5 ± 1.2 | NQ | NQ | 1.0 ± 0.1 | 47.7 ± 3.3 | 0.4 ± 0.1 | 3.8 ± 0.3 | ||||||
NQ, not quantifiable.
↵ a Compound is a CAR activator (Maglich et al., 2003; Simonsson et al., 2006).
↵ b Gene induction occurs via cross-talk between PXR and CAR (Wang et al., 2004; Trubetskoy et al., 2005; Bell and Michalopoulos, 2006).
↵ c Dose-response curve did not reach saturation for CYP3A4 induction within concentrations tested.
↵ d Compound is a PXR-activator (LeCluyse, 2001; Luo et al., 2002; van Giersbergen et al., 2002).
↵ e Compound is a PXR activator (EC50 = 1.7 ± 0.3 μM; N Hariparsad, unpublished data).
↵ f High S.E.