F2 values, -fold induction at highest concentration tested (given in parenthesis), and AUC/F2 for induction of CYP3A4 mRNA in HepaRG cells treated with rifampicin, omeprazole, troglitazone, phenytoin, primaquine, phenobarbital, carbamazepine, dexamethasone, hyperforin, nifedipine, or sulfinpyrazone F2 is the concentration resulting in a 2-fold increase of baseline mRNA levels. EC50 values are presented when achieved. Values are mean ± S.D. of three separate batches of differentiated HepaRG cells. Published values of in vivo exposure (AUC) for the same drugs are listed.
F2 | -Fold Induction at Highest Concentration | AUC/F2 | In Vivo AUC | Reference in Vivo AUC | |
|---|---|---|---|---|---|
| Rifampicin | 0.13 ± 0.10a | 24 ± 12 (4 μM) | 262 | 34.1b | Polk et al., 2001 |
| (EC50 = 0.25 ± 0.02a) | |||||
| Omeprazole | 2.0 ± 0.33 | 12 ± 2.2 (40 μM) | 0.54 | 1.11 | Andersson et al., 1998 |
| Troglitazone | 0.56 ± 0.20 | 11 ± 6.0 (6.25 μM) | 29.5 | 16.5 | Ott et al., 1998 |
| Phenytoin | 2.2 ± 1.8 | 3.4 ± 2.3 (40 μM) | 218 | 468 | Spaans et al., 2002 |
| Primaquine | N.I.c | N.I. | N.I. | 3.27 | Na-Bangchang et al., 2000 |
| Phenobarbital | 15 ± 3.9 | 14 ± 4.0 (200 μM) | 98.5 | 1497 | Reidenberg et al., 1995 |
| Carbamazepine | 5.5 ± 1.8 | 16 ± 3.8 (250 μM) | 228 | 1248 | Olling et al., 1999 |
| Dexamethasone | 2.8 ± 0.34 | 23 ± 4.0 (250 μM) | 0.10 | 0.29 | Loew et al., 1986 |
| Hyperforin | 0.04 ± 0.005 | 15 ± 5.8 (0.04 μM) | 168 | 6.24 | Biber et al., 1998 |
| Nifedipine | 1.6 ± 0.1 | 22 ± 5.4 (62.5 μM) | 0.30 | 0.49 | Hippius et al., 1995 |
| Sulfinpyrazone | 2.1 ± 1.0 | 24 ± 13 (250 μM) | 134 | 287 |
Schlicht et al., 1985
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