Median induction parameters EC50 (μM) and Emax from mRNA levels after treatment with CD 6168 in three human hepatocyte donors
| P450 Isoform | CD 6168 or Deleobuvir-AGa | Prototypical Inducerc | |||||
|---|---|---|---|---|---|---|---|
| EC50 (μM) | Emax Fold | Emax/EC50 | EC50 (μM) | Emax Fold | Emax/EC50 | ||
| Total | Freeb | ||||||
| CYP1A2a | 6.2 | 0.71 | 6.7 | 9.4 | 11.9 | 20.4 | 1.7 |
| CYP2B6 | 1.1 | 0.18 | 3.8 | 21 | 595 | 10.2 | 0.017 |
| CYP2C8 | 2.7 | 0.43 | 5.9 | 14 | NC | 5.1 | NC |
| CYP2C9 | 0.25 | 0.040 | 2.1 | 53 | NC | 2.5 | NC |
| CYP3A4 | 0.39 | 0.058 | 12.4 | 214 | 0.813 | 26.8 | 33 |
NC, not calculable, the dynamic range was insufficient to generate non-ambiguous fitting parameters therefore the Emax reported is the maximal fold change observed over the rifampicin incubation concentrations.
↵a CYP1A2 induction parameters are from deleobuvir-AG incubations; for other isoforms parameters are from CD 6168 incubations.
↵b Adjusted for protein binding in induction media which contains bovine serum albumin in the insulin, transferrin and selenium ITS supplement.
↵c Prototypical inducers were omeprazole (CYP1A2), phenobarbital (CYP2B6), and rifampicin (CYP2C8, CYP2C9, and CYP3A4).