Comparison of in vitro and in vivo formation of M2a, M2b and estimation of enzyme kinetics based on in vitro formation of M2a, M2b, and faldaprevir glucuronide in human HepatoPac
| Parameter | Metabolite of Interest | ||
|---|---|---|---|
| M2a | M2b | Faldaprevir Glucuronide | |
| Comparison of in vitro and in vivo formation rates | |||
| In vivo formation (pmol/min/total liver) | 5912 | 5310 | Not detected |
| In vitro formation (pmol/min/total liver) | 3714–15,816 | 6933–26,473 | 1405–5771 |
| Enzyme kinetics estimation from in vitro incubations with human HepatoPac | |||
| Km (μM) | 0.233 ± 0.034 | 0.205 ± 0.027 | 0.671 ± 0.10 |
| Vmax (pmol/min/total liver) | 225,486 ± 11,079 | 356,585 ± 15,275 | 211,055 ± 15,915 |
| CLint (ml/min) at 120-mg QD dose (Fm pathway) | 2579 (89%) | 311 (11%) | |
| CLint (ml/min) at 240-mg QD dose (Fm pathway) | 2195 (88%) | 294 (12%) | |
| Comparison of Km generated from HLM and human HepatoPac | |||
| Km (μM) from HLMa | 4.60 | 4.79 | — |
| Ratio of Km determined from HLM vs. HepatoPac | 19.7 | 23.4 | — |
—, comparison not made
↵a Li et al., 2014.