Title of article :
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
Author/Authors :
Zhu, Songlin Department of Clinical Pharmaceutical Research Institution - Hunan Cancer Hospital - Affliated Tumor Hospital of Xiangya Medical School of Central South University - Changsha, Hunan, China , Deng, Jun Department of Clinical Pharmaceutical Research Institution - Hunan Cancer Hospital - Affliated Tumor Hospital of Xiangya Medical School of Central South University - Changsha, Hunan, China , Tang, Qi Department of Clinical Pharmaceutical Research Institution - Hunan Cancer Hospital - Affliated Tumor Hospital of Xiangya Medical School of Central South University - Changsha, Hunan, China , Heng, Jianfu Department of Clinical Pharmaceutical Research Institution - Hunan Cancer Hospital, Affliated Tumor Hospital of Xiangya Medical School of Central South University - Changsha, Hunan, China , Qu, Jingjing Department of Early Clinical Trail Center - Hunan Cancer Hospital - Affliated Tumor Hospital of Xiangya Medical School of Central South University - Changsha, Hunan, China , Chen, Yong Department of Early Clinical Trail Center - Hunan Cancer Hospital - Affliated Tumor Hospital of Xiangya Medical School of Central South University - Changsha, Hunan, China , Li, Kunyan Department of Early Clinical Trail Center - Hunan Cancer Hospital - Affliated Tumor Hospital of Xiangya Medical School of Central South University - Changsha, Hunan, China , Yang, Nong Department of Lung Cancer and Gastroenterology - Hunan Cancer Hospital - Affliated Tumor Hospital of Xiangya Medical School of Central South University - Changsha, Hunan, China , Liu, Xiaobao Department of Clinical Pharmaceutical Research Institution - Hunan Cancer Hospital, Affliated Tumor Hospital of Xiangya Medical School of Central South University - Changsha, Hunan, China
Abstract :
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 signifcant 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
signifcant 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 , Pharmacokinetics , Healthy volunteers , Bioavailability , High-fat meal
