The aim of the study was to study the PK of AST2818 tablets after one oral dose in healthy male subjects on an empty stomach and in a postprandial state and to evaluate the effect of food on AST2818 bioavailability. Sixteen healthy Chinese male subjects were randomly divided into two groups: a fasting-postprandial group and a postprandial-fasting group. The drug was administered once per evaluation at a dose of 80 mg, with an interval of 22 days between the two treatments. The LC-MS/MS method was used to determine the concentrations of AST2818 and its metabolite AST5902. Plasma pharmacokinetic parameters were calculated by noncompartmental analysis (NCA). WinNonlin® version 7.0 was used to analyse PK parameters, and SAS version 9.4 was used for statistical analyses. After a meal, the peak concentration of alflutinib increased by approximately 53%, and the AUC increased by approximately 32%; The peak concentration of its metabolite AST5902 decreased by approximately 20%, and the AUC decreased by approximately 8%. There was no significant change in peak time. The peak AST5902 concentration and AUC0-∞ were 27.4% and 71.4%, respectively, of that of alflutinib. None of the subjects experienced serious AEs, and both fasting and high-fat meal administration were safe. There was no statistically significant difference between groups in AEs (P = 0.102, RR = 1.40) or adverse reactions (P = 0.180, RR = 1.30). The effects of food may not need to be considered for the clinical use of alflutinib. No serious AEs occurred, and drug administration was safe and tolerable after fasting or a high-fat meal.
Keywords: Alflutinib mesylate tablets; Bioavailability; Healthy volunteers; High-fat meal; Pharmacokinetics.