Lymphoid depletion in rat spleen (≥25 mg/kg/day), lymph nodes and thymus (≥200 mg/kg/day)
“Lymphoid depletion was observed at ≥25 mg/kg/day in the 4-week study in spleen, and also in lymph nodes and thymus at ≥200 mg/kg/day in the 4-week 2x2 intermittent dosing and 14-day studies.”
“In addition, after repeated oral doses brain-to-plasma concentration ratios of entrectinib were higher at 24 hours post last dose in mice (~0.4), rats (0.6–1.5), and dogs (1.4-2.2), indicating brain penetration occurred under steady-state conditions.”
“In the 4-week (2x2 intermittent dosing) study, moderate prolongation of the QT/QTcF intervals was noted at 120 mg/kg/day (recorded on Day 11), where a Cmax of >7 µM was observed.”