Summary of in vitro induction parameters from test compound concentration/fold change in CYP3A4 mRNA curves obtained with HepaRG cells (three experiments)
| Test Drug | CYP3A4 mRNA Expression | ||||
|---|---|---|---|---|---|
| HepaRG (Replicate 1) | HepaRG (Replicate 2) | HepaRG (Replicate 3) | Mean HepaRG | S.D. HepaRG | |
| Carbamazepine | |||||
| EC50 (µM) | 59 | 40 | 27 | 42 | 16 |
| Emax (FI) | 7.1 | 7.1 | 4.3 | 6.2 | 1.6 |
| Nifedipine | |||||
| EC50 (µM) | 16 | 9.3 | 14 | 13 | 3.5 |
| Emax (FI) | 5.5 | 6.9 | 3.6 | 5.3 | 1.7 |
| Phenytoin | |||||
| EC50 (µM) | 31 | 46 | 37 | 38 | 7.3 |
| Emax (FI) | 6.9 | 7.3 | 4.9 | 6.4 | 1.3 |
| SARA | |||||
| EC50 (µM) | 4.1 | 2.7 | 2.5 | 3.1 | 0.87 |
| Emax (FI) | 9.9 | 9.7 | 6.2 | 8.6 | 2.1 |
| SARB | |||||
| EC50 (µM) | 12 | 3.9 | 11 | 8.9 | 4.4 |
| Emax (FI) | 8.4 | 5.9 | 7.2 | 7.1 | 1.3 |
| Pioglitazone | |||||
| EC50 (µM) | 25 | 25 | 16 | 22 | 5.2 |
| Emax (FI) | 4.4 | 3.8 | 2.7 | 3.6 | 0.85 |
| Rifampicin | |||||
| EC50 (µM) | 2.2 | 3.2 | 1.8 | 2.4 | 0.77 |
| Emax (FI) | 17 | 17 | 16 | 17 | 0.33 |
| Rifapentine | |||||
| EC50 (µM) | 0.66 | 1.0 | 1.8 | 1.2 | 0.57 |
| Emax (FI) | 12 | 12 | 14 | 12 | 1.1 |
| Phenobarbital | |||||
| EC50 (µM) | 309 | 322 | 343 | 325 | 17 |
| Emax (FI) | 9.6 | 9.8 | 8.1 | 9.2 | 0.90 |
| Troglitazone | |||||
| EC50 (µM) | 7.6 | 12 | 4.1 | 7.8 | 3.8 |
| Emax (FI) | 2.2 | 3.0 | 2.4 | 2.5 | 0.41 |
| Rosiglitazone | |||||
| EC50 (µM) | 9.8 | 8.9 | 9.7 | 9.5 | 0.49 |
| Emax (FI) | 3.9 | 4.3 | 4.2 | 4.1 | 0.24 |
| SARC | |||||
| EC50 (µM) | 7.7 | 6.3 | 8.5 | 7.5 | 1.1 |
| Emax (FI) | 8.5 | 7.9 | 6.0 | 7.4 | 1.3 |
| SARD | |||||
| EC50 (µM) | 4.3 | 5.2 | 4.0 | 4.5 | 0.64 |
| Emax (FI) | 6.7 | 6.7 | 4.4 | 5.9 | 1.3 |
| Pleconaril | |||||
| EC50 (µM) | 23 | 31 | 43 | 32 | 10 |
| Emax (FI) | 2.1 | 3.3 | 4.2 | 3.2 | 1.0 |
| Aprepitant | |||||
| EC50 (µM) | 1.4 | 1.7 | 4.0 | 2.4 | 1.4 |
| Emax (FI) | 3.1 | 4.7 | 2.8 | 3.6 | 1.0 |
FI, fold induction.