Effects of meal type on the oral bioavailability of the ALK inhibitor ceritinib in healthy adult subjects.

摘要: Ceritinib is a potent inhibitor of anaplastic lymphoma kinase (ALK), which has shown acceptable safety and substantial antitumor activity in ALK-positive non-small cell lung cancer (NSCLC) patients. Two food-effect studies were conducted healthy adults to investigate the influence food on oral bioavailability ceritinib: study with low- or high-fat meals at 500 mg light snack 750 mg. Compared fasted state, AUC0-∞ (90%CI) ceritinib was increased by 58% (34%, 86%) after intake low-fat meal, 73% (46%, 105%) 54% (19%, 99%) snack. Safety assessments also suggested that may improve gastrointestinal (GI) tolerability single dose. Based pharmacokinetic results, it essential avoid any type meal during dosing because increase occurrence exposure-dependent, non-GI toxicities labeled dose 750 mg daily fasting. A randomized trial ongoing determine an alternative way give (450 mg 600 mg food) enhance GI NSCLC