Overview of studies using organotypic liver cultures for hepatic clearance predictions
Number of Compounds Predicted within 2-Fold of In Vivo Cl | |||||
---|---|---|---|---|---|
Culture Paradigm | Low-Clearance Compounds | Medium- to High-Clearance Compounds | Prediction Method | Results/Conclusion | Reference |
PHH in MPCC | 7/10 | 4/7 | Conventional | Medium- to high-Cl compounds mainly underpredicted | (Chan et al., 2013) |
PHH in MPCC | 9/15 | 3/10 | Conventional | High-Cl compounds underpredicted | (Da-silva et al., 2018) |
PHH in MPCC | 5/8 | — | Direct scaling | No clear tendency | (Kratochwil et al., 2017) |
PHH in MPCC | 4/12 | 2/3 | Conventional | Clinical drug candidates (low Cl) were better predicted using direct scaling | (Kratochwil et al., 2017) |
PHH spheroids | 2/3 | 1/3 | Conventional | Compounds were underpredicted | (Kanebratt et al., 2021) |
PHH in chip | 0/2 | 3/4 | Direct scaling | Low-Cl compounds below LOQ, high Cl underpredicted | (Chao et al., 2009) |
Cl, clearance; LOQ, limit of quantification.