Summary of estimated parameter values for glyburide and metabolites in the SCHH model (mean and 95% CI)
| CLu,act | CLu,pass | CLu,bile | CLu,efflux | fu,c | |
|---|---|---|---|---|---|
| µl · min−1 · mg protein−1 | |||||
| Glyburide | 11.8 (9.0–16) | 13.8 (9.3–15) | 1.9 (1.4 × 10−5 to 3.6) | 5.5 × 10−5 (7.9 × 10−7 to 1.7) | 0.0301a (fixed) |
| M1 | 3.61 (2.4–7.2) | 0.661b (0.33–2.9) | 0.222 (1.9 × 10−9 to 0.71) | 0.634 (1.9 × 10−8 to 3.1) | 0.579a,b (fixed) |
| M2b | 7.20 (4.6–11) | 0.0866 (6.7 × 10−8 to 1.5) | 1.14 (4.7 × 10−9 to 2.7) | ||
↵a fu,c was estimated from PHHs after longer incubations (Supplemental Fig. 1).
↵b Assumed to be the same for both metabolites to minimize overparameterization of the mechanistic model used to estimate in vitro transport kinetics in hepatocyte systems.