Trametinib PK parameters in FVBn-WT, Mdr1a/b−/−, Bcrp1−/−, and Mdr1a/b−/− Bcrp1−/− (triple knockout) after 5 mg/kg i.v. dose
| PK Parameters | Trametinib 5 mg/kg i.v. | |||||||
|---|---|---|---|---|---|---|---|---|
| Wild-type | Bcrp1−/− | Mdr1a/b−/− | Mdr1a/b−/−Bcrp1−/− | |||||
| Plasma | Brain | Plasma | Brain | Plasma | Brain | Plasma | Brain | |
| Terminal rate constant (hr–1) | 0.15 | 0.12 | 0.11 | 0.15 | ||||
| Half-life (hr) | 4.7 | 5.6 | 6.3 | 4.8 | ||||
| Clearance (ml/hr) | 5.1 | 6.1 | 4.7 | 5.2 | ||||
| Volume (ml) | 37.3 | 49.6 | 42.9 | 36.1 | ||||
| AUC (0–tlast) μg-hr/ml | 26.8 ± 2.8 | 4.0 ± 0.43 | 23.0 ± 0.11 | 3.1 ± 0.30 | 29.2 ± 1.7 | 21.4 ± 0.93 | 27.8 ± 1.6 | 18.8 ± 0.87 |
| Kp (AUCbrain/AUCplasma) | 0.15 | 0.14 | 0.73 | 0.68 | ||||
| Kp ratio (Kp knockout/Kp wild type) | 0.92* | 4.9* | 4.6* | |||||
↵*, ratio of ratios