Total cellular tyrosine kinase inhibitor (TKI) concentrations, fraction bound, and unbound TKI concentrations in three lots of SCHH compared with published BSEP IC50 values.
| Cellular TKI Concentrations (µM, Mean ± standard deviation) | |||
|---|---|---|---|
| Lot/TKI | Dasatinib | Pazopanib | Sorafenib |
| EGO | 27 ± 10 | 288 ± 30 | 517 ± 41 |
| RVQ | 51 ± 5 | 257 ± 11 | 587 ± 36 |
| WID | 5 ± 1 | 213 ± 19 | 296 ± 17 |
| Cellular Fraction Unbound (fu,cell) | 0.0092 | 0.0064 | 0.0010 |
| EGO (unbound) | 0.25 ± 0.09 | 1.84 ± 0.19 | 0.52 ± 0.04 |
| RVQ (unbound) | 0.47 ± 0.05 | 1.64 ± 0.07 | 0.59 ± 0.04 |
| WID (unbound) | 0.05 ± 0.01 | 1.36 ± 0.12 | 0.30 ± 0.02 |
| Reported BSEP IC50a | 13.1 | 10.3 | 8.0 |
BID, twice daily dosing; QD, daily dosing.
a (Morgan et al., 2010; Morgan et al., 2013)