The pharmacokinetic/metric parameters of panRAF inhibitors in FVB WT mice following administration of a single intravenous dose of 5 mg/kg
Data are presented as mean or mean ± S.E.M. (n = 4).
| Parameter | CCT196969 | LY3009120 | MLN2480 | |||
|---|---|---|---|---|---|---|
| Plasma | Brain | Plasma | Brain | Plasma | Brain | |
| Half-life (h) | 2.79 | 3.37 | 2.35 | 1.74 | 6.54 | 7.25 |
| AUC(0–t) (µg⋅h/ml) | 150.23 ± 6.08 | 0.92 ± 0.02 | 10.86 ± 0.59 | 0.51 ± 0.03 | 17.56 ± 0.47 | 3.45 ± 0.09 |
| AUC(0–∞) (µg⋅h/ml) | 155.07 | 0.97 | 10.88 | 0.51 | 22.71 | 4.49 |
| CL (ml/min per kilograms) | 0.54 | — | 7.66 | — | 3.7 | — |
| Vd (l/kg) | 0.13 | — | 1.56 | — | 2.08 | — |
| Kp (AUC(0–∞) ratio) | — | 0.006 | — | 0.05 | — | 0.20 |
| Kp,uu (AUC(0–∞) ratio) | — | 0.03 | — | 0.02 | — | 0.05 |
AUC(0–t), area under the curve from zero to the time of the last measured concentration; AUC(0–∞), area under the curve from zero to time infinity; CL, clearance; Kp, ratio of AUC(0–∞,brain) to AUC(0–∞,plasma) using total drug concentrations; Kp,uu, ratio of AUC(0–∞,brain) to AUC(0–∞,plasma) using free drug concentrations; Vd, volume of distribution.
—, not relevant in these tissues.