Summary of in vitro induction parameters from test compound concentration/fold change in CYP3A4 mRNA curves obtained with the six human cryopreserved hepatocyte batches
| Test Drug | CYP3A4 mRNA Expression | |||||||
|---|---|---|---|---|---|---|---|---|
| CD-Hu4237 | BD-295 | IVT-IBG | BD-281 | CD-Hu8084 | HH1024 | Mean | S.D. | |
| Carbamazepine | ||||||||
| EC50 (µM) | 35 | 59 | 36 | 98 | 95 | 29 | 59 | 31 |
| Emax (FI) | 19 | 15 | 9.3 | 13 | 19 | 21 | 16 | 4.4 |
| Nifedipine | ||||||||
| EC50 (µM) | 12 | 13 | 13 | 66 | 23 | 14 | 23 | 21 |
| Emax (FI) | 14 | 41 | 9.1 | 9.1 | 15 | 30 | 20 | 13 |
| Phenytoin | ||||||||
| EC50 (µM) | 13 | 12 | 32 | 38 | 41 | 10 | 24 | 14 |
| Emax (FI) | 15 | 8.7 | 9.1 | 7.3 | 6.8 | 10 | 9.5 | 3.0 |
| SARA | ||||||||
| EC50 (µM) | 1.7 | 3.2 | 2.4 | 7.5 | ND | ND | 3.7 | 2.6 |
| Emax (FI) | 15 | 8.9 | 2.6 | 5.8 | ND | ND | 8.0 | 5.1 |
| SARB | ||||||||
| EC50 (µM) | 4.3 | 3.3 | 4.2 | 7.6 | 11 | 3.1 | 5.6 | 3.1 |
| Emax (FI) | 14 | 15 | 5.3 | 3.2 | 5.7 | 10 | 8.9 | 4.9 |
| Pioglitazone | ||||||||
| EC50 (µM) | 13 | 11 | 12 | 29 | 21 | 10 | 16 | 7.5 |
| Emax (FI) | 4.3 | 7.9 | 4.3 | 12 | 10 | 4.3 | 7.2 | 3.5 |
| Rifampicin | ||||||||
| EC50 (µM) | 0.32 | 0.94 | 0.62 | 1.1 | 2.8 | 0.40 | 1.0 | 0.91 |
| Emax (FI) | 30 | 141 | 24 | 30 | 50 | 65 | 57 | 44 |
| Rifapentine | ||||||||
| EC50 (µM) | 0.42 | 2.1 | 0.89 | 2.6 | 1.4 | 0.61 | 1.3 | 0.86 |
| Emax (FI) | 25 | 122 | 15 | 23 | 22 | 55 | 44 | 41 |
| Phenobarbital | ||||||||
| EC50 (µM) | 261 | 240 | 239 | 338 | 480 | 300 | 310 | 92 |
| Emax (FI) | 26 | 89 | 14 | 19 | 21 | 36 | 34 | 28 |
| Troglitazone | ||||||||
| EC50 (µM) | 2.9 | 1.6 | 4.1 | 3.9 | 4.4 | 2.4 | 3.2 | 1.1 |
| Emax (FI) | 26 | 68 | 21 | 22 | 35 | 55 | 38 | 19 |
| Rosiglitazone | ||||||||
| EC50 (µM) | 14 | 11 | 16 | 16 | 17 | 13 | 14 | 2.0 |
| Emax (FI) | 12 | 5.8 | 7.3 | 14 | 19 | 19 | 13 | 5.7 |
| SARC | ||||||||
| EC50 (µM) | 5.4 | 2.8 | 5.9 | 9.3 | 2.8 | 6.0 | 5.4 | 2.4 |
| Emax (FI) | 25 | 37 | 14 | 18 | 31 | 24 | 25 | 8.6 |
| SARD | ||||||||
| EC50 (µM) | 3.8 | 6.7 | 12 | 5.3 | ND | 6.4 | 6.8 | 3.0 |
| Emax (FI) | 14 | 13 | 4.7 | 28 | ND | 14 | 15 | 8.3 |
| Pleconaril | ||||||||
| EC50 (µM) | 13 | 11 | 23 | ND | ND | ND | 16 | 6.7 |
| Emax (FI) | 5.9 | 12 | 2.8 | ND | ND | ND | 7.0 | 4.8 |
| Aprepitant | ||||||||
| EC50 (µM) | ND | ND | ND | 3.5 | 2.3 | 3.1 | 3.0 | 0.61 |
| Emax (FI) | ND | ND | ND | 10 | 6.5 | 7.6 | 8.1 | 2.0 |
FI, fold induction; ND, not determined.