Table 1.
Plasma and organ pharmacokinetic parameters of selpercatinib in male wild-type, Abcb1a/1b; Abcg2-/- and Slco1a/1b-/- mice over 4 h after oral administration of 10 mg/kg selpercatinib.
| Parameter | Genotype | ||
|---|---|---|---|
| Wild-Type | Abcb1a/1b;Abcg2-/- | Slco1a/1b-/- | |
| AUC0–4h, ng/mL*h | 26,649 ± 6360 | 30,188 ± 7632 | 36,197 ± 5255 |
| Fold change AUC0–4h | 1.0 | 1.1 | 1.4 |
| Cmax, ng/mL | 7862 ± 1814 | 8582 ± 2160 | 11,625 ± 1614 * |
| Tmax, h | 1.8 ± 1.2 | 1.6 ± 1.2 | 1.7 ± 0.52 |
| Cbrain, ng/g | 186 ± 23 | 3454 ± 855 *** | 278 ± 42 ** |
| Fold increase Cbrain | 1.0 | 18.6 | 1.5 |
| Brain-to-plasma ratio | 0.030 ± 0.004 | 0.46 ± 0.04 *** | 0.038 ± 0.005 ** |
| Fold increase ratio | 1.0 | 15.3 | 1.3 |
| Cliver, ng/g | 17,593 ± 3471 | 19,077 ± 2696 | 19,916 ± 3174 |
| Fold increase Cliver | 1.0 | 1.1 | 1.1 |
| Liver-to-plasma ratio | 2.8 ± 0.4 | 2.6 ± 0.3 | 2.7 ± 0.4 |
| Fold increase ratio | 1.0 | 0.93 | 1.0 |
| CSIC, ng/g | 91,051 ± 22,029 | 34,929 ± 16,659 * | 140,998 ± 48,076 |
| Fold change CSIC | 1.0 | 0.38 | 1.5 |
| SIC-to-plasma ratio | 14.9 ± 4.1 | 4.5 ± 1.8 *** | 19.0 ± 5.3 |
| Fold increase ratio | 1.0 | 0.30 | 1.3 |
| Ctestis, ng/g | 730 ± 103 | 5726 ± 1535 *** | 1121 ± 107 ** |
| Fold increase Ctestis | 1.0 | 7.8 | 1.5 |
| Testis-to-plasma ratio | 0.12 ± 0.02 | 0.76 ± 0.13 *** | 0.15 ± 0.01 * |
| Fold increase ratio | 1.0 | 6.3 | 1.3 |
AUC0–4h, area under plasma concentration–time curve; Cmax, maximum concentration in plasma; Tmax, time point (h) of maximum plasma concentration; Cbrain, brain concentration; Cliver, liver concentration; SIC, small intestine contents; CSIC, small intestine contents concentration; Ctestis, testis concentration; Data are given as mean ± S.D. (n = 6–7). *, p < 0.05; **, p < 0.01; ***, p < 0.001 compared to wild-type mice. Statistical analysis was applied after log-transformation of linear data.