TABLE 7

Rat brain uptake assay results for abemaciclib and palbociclib in Sprague-Dawley rats

Rats were dosed intravenously with vehicle (control) or vehicle containing 30 mg/kg of the P-gp inhibitor LSN335984 (+ Inhibitor) at 1 h before dosing with test compound at 2.2 ยตmol/kg. Total concentrations in plasma and brain were measured 5 minutes after intravenous dose. Brain concentrations were corrected for plasma volume and unbound concentrations were calculated using the measured unbound fraction (Table 4).

CompoundCu,plasmaCu,brainKp,brainKp,uu,brain
Control+ InhibitorControl+ InhibitorControl+ InhibitorControl+ Inhibitor
nM
Abemaciclib928810391.33.90.110.44
Palbociclib3274644320.12.30.010.07
  • Kp,brain, brain-to-plasma ratio of the total concentrations; Kp,uu,brain, brain-to-plasma ratio of the unbound concentrations.