Effect of Food on the Pharmacokinetics of Quizartinib

Quizartinib is an oral, highly potent, and selective type II FMS-like tyrosine kinase 3 inhibitor in development for acute myeloid leukemia. This parallel-group study evaluated potential food effects on quizartinib absorption in healthy subjects who received a single 30-mg dose after overnight fasting (n = 34) or a high-fat, high-calorie meal (n = 30). Blood samples were collected through 504 hours after dosing, and pharmacokinetic parameters calculated were maximum observed concentration (C_max ) and area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUC_last ) and from time 0 to infinity (AUC_inf ). Mean quizartinib pharmacokinetic profiles were similar under fasted and fed conditions. The geometric least squares means ratios (%) for fed/fasted and associated 90% confidence intervals (CIs) for C_max , AUC_last , and AUC_inf were 91.58 (82.15-102.08), 105.39 (90.79-122.35), and 108.39 (91.54-128.34), respectively. The 90%CI for the ratio fell within the 80% to 125% limits for C_max and AUC_last , with 90%CI for AUC_inf slightly outside the limits (ie, 128%). Food delayed quizartinib time to C_max by 2 hours. All adverse events were either mild or moderate; no discontinuations due to adverse events occurred. Based on these results, quizartinib can be administered without regard to food.