A Randomized Open Single-Centre Crossed Study of the Effect of Food on the Pharmacokinetics of One Oral Dose of Alflutinib Mesylate Tablets (AST2818) in Healthy Male Subjects

摘要

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.