Emax in CYP3A4 mRNA and testosterone 6β-hydroxylase activity for 20 clinical inducers in three lots of cryopreserved human hepatocytes from different donors
| Drug | Hu4026 | RCP | Hu8020 | Average Means | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| mRNA | Activity | Ratio | mRNA | Activity | Ratio | mRNA | Activity | Ratio | Mean | SD | |
| Aprepitant (0.1–10 μM) | 15 | 0.7 | 21 | 12 | 0.6 | 19 | 7.6 | 0.5 | 15.3 | 19 | 3 |
| Avasimibe (0.1–10 μM) | 14 | 1.0 | 14 | 14 | 1.7 | 8.4 | 28 | 32 | 0.9 | 7.8 | 6.6 |
| Bosentan (0.4–100 μM) | 54 | 12 | 4.5 | 38 | 5.1 | 7.3 | 5.6 | 8.0 | 0.7 | 4.2 | 3.3 |
| Carbamazepine (5–250 μM) | 40 | 8.7 | 4.6 | 7.6 | 2.3 | 3.3 | 23 | 14 | 1.7 | 3.2 | 1.4 |
| Efavirenz (0.1–10 μM) | 22 | 9.8 | 2.3 | 10 | 11 | 0.9 | 25 | 23 | 1.1 | 1.4 | 0.73 |
| Ethinyl estradiol (1–100 μM) | 53 | 4.2 | 13 | 16 | 2.1 | 7.6 | N.A. | N.A. | N.A. | 10 | 4 |
| Hyperforin (0.1–5 μM) | 26 | 5.4 | 4.8 | 12 | 4.8 | 2.5 | N.A. | N.A. | N.A. | 3.7 | 1.6 |
| Modafinil (0.1–100 μM) | 7.0 | 7.5 | 0.93 | 12 | 6.0 | 2.0 | 8.3 | 8.8 | 1.0 | 1.3 | 0.6 |
| Nafcillin (0.1–100 μM) | 6.1 | 1.5 | 4.1 | 14 | 3.6 | 3.9 | 22 | 3.1 | 7.2 | 5.0 | 1.9 |
| Nevirapine (0.1–100 μM) | 21 | 1.3 | 16 | 6.7 | 1.3 | 5.0 | 21 | 4.0 | 5.2 | 8.8 | 6.5 |
| Oxcarbazepine (0.1–100 μM) | 7.9 | 1.4 | 5.6 | 5.2 | 1.7 | 3.0 | 16 | 18 | 0.9 | 3.2 | 2.4 |
| Phenobarbital (10–2000 μM) | 55 | 26 | 2.2 | 15 | 10 | 1.4 | 38 | 9.8 | 3.9 | 2.5 | 1.2 |
| Phenytoin (1–250 μM) | 18 | 6.6 | 2.8 | 19 | 17 | 1.2 | 25 | 15 | 1.7 | 1.9 | 0.83 |
| Pleconaril (0.1–100 μM) | 15 | 4.1 | 3.8 | 14 | 3.3 | 4.3 | 21 | 4.5 | 4.6 | 4.3 | 0.44 |
| Rifabutin (0.1–100 μM) | 48 | 6.2 | 7.7 | 27 | 12.0 | 2.3 | 25 | 22 | 1.1 | 3.7 | 3.5 |
| Rifampin (0.01–50 μM) | 67 | 24 | 2.8 | 40 | 17 | 2.4 | 59 | 38 | 1.6 | 2.2 | 0.63 |
| Sulfinpyrazole (0.1–100 μM) | 38 | 4.8 | 7.9 | 19 | 3.3 | 5.6 | 40 | 54 | 0.8 | 4.8 | 3.7 |
| Terbinafine (10–30 μM) | 3.3 | 1.0 | 3.3 | 16 | 8.9 | 1.8 | 12 | 18 | 0.7 | 1.9 | 1.32 |
| Topiramate (0.1–100 μM) | 5.9 | 1.7 | 3.6 | 5.1 | 1.6 | 3.3 | 9.0 | 7.1 | 1.3 | 2.7 | 1.2 |
| Troglitazone (0.1–50 μM) | 23 | 6.3 | 3.6 | 6.3 | 3.8 | 1.6 | 28 | 6.9 | 4.0 | 3.1 | 1.3 |
| Averages | 6.4 ± 5.4 | 4.3 ± 4.1 | 3.0 ± 3.6 | 4.7 ± 4.1 | |||||||
N.A., not available.