Uptake and metabolism kinetic parameters of repaglinide estimated in three human hepatocyte donors using an extended mechanistic two-compartment model
Uptake kinetics was measured in cryopreserved human hepatocytes plated for 6 h at seven concentrations (0.1–300 μM) in the presence (HU4122) or absence (HU4199 and HU8089) of 1 mM ABT.
| Donor | HU4122 | HU4199 | HU8089 | Mean |
|---|---|---|---|---|
| Km, u, μM | 15.6 | 8.97 | 13.8 | 12.8 ± 3.4 |
| Vmax, pmol · min−1 · 106 cells−1 | 1236 | 310 | 464 | 670 ± 496 |
| Pdiff, u, μl · min−1 · 106 cells−1 | 10.0 | 16.0 | 12.0 | 12.7 ± 3.1 |
| fucella | 0.074 | 0.074 | 0.074 | 0.074 |
| fumed | 0.95 | 0.94 | 0.96 | 0.95 ± 0.01 |
| CLactive, u, μl · min−1 · 106 cells−1 | 79.0 | 34.6 | 33.6 | 49.1 ± 25.9 |
| CLmet, gluc, u, μl · min−1 · 106 cells−1 | 0.412 | 0.242 | 0.327 | |
| Km, M2, u, μM | 41.5 | 7.40 | 24.4 | |
| CLmet, M2, u, μl · min−1 · 106 cells−1 | 0.950 | 2.42 | 1.68 | |
| Km, M4, u, μM | 5.32 | 8.83 | 7.07 | |
| CLmet, M4, u, μl · min−1 · 106 cells−1 | 0.619 | 1.29 | 0.957 | |
| CLmet,t otal, u, μl · min−1 · 106 cells−1 | 1.98 | 3.96 | 2.97 |
↵a Data from uptake experiments performed in rat hepatocytes over an extended incubation time (Ménochet et al., 2012).