Uptake and metabolism kinetic parameters of repaglinide estimated in rat hepatocytes by using an extended two-compartment mechanistic model
Uptake kinetics was measured in freshly isolated rat hepatocytes plated for 2 h over 45 min at 10 concentrations (0.1–300 μM).
| Scenario 1, +ABT, repaglinide and repaglinide glucuronide cell concentrations (n = 1) | Scenario 2, − ABT, repaglinide, repaglinide glucuronide and M2 cell concentrations (n = 1) | Scenario 3, − ABT, repaglinide, repaglinide glucuronide and M2 cell concentrations (n = 1) | |
|---|---|---|---|
| Km,u, μM | 10.0 | 11.0 | 15.0 |
| Vmax, pmol/min/106 cells | 857 | 1315 | 903 |
| Pdiff,u, μl/min/106 cells | 13.1 | 35.7 | 27.2 |
| fucell | 0.051 | 0.074 | 0.058 |
| CLactive,u, μl/min/106 cells | 85.9 | 119 | 60.2 |
| CLmet,M2,u μl/min/106 cells | — | 0.434 | 0.546 |
| Km,gluc,u, μM | — | — | 12.0 |
| Vmax,gluc, pmol/min/106 cells | — | — | 17.0 |
| CLmet,gluc,u, μl/min/106 cells | 0.901 | 0.630 | 1.412 |
| Maximal proportion of active transport, % | 86.7 | 77.0 | 68.9 |
—, no data.