中国临床药理学杂志2024，Vol.40Issue(16)：2378-2382,5.DOI:10.13699/j.cnki.1001-6821.2024.16.016
依折麦布片在中国健康受试者中的生物等效性研究
Bioequivalence study of ezetimibe tablets in Chinese healthy subjects
赵沛月 1兰静 2梁文忠 2张天财 1张豫宁 1李亚飞 1赵守仁 1贺建昌 3董丽春 3孙敏 1胡艳君2
作者信息
- 1. 云南省药物研究所,云南昆明 650111||云南省中药和民族药新药创制企业重点实验室,云南昆明 650111
- 2. 上海药明康德新药开发有限公司,上海 200131
- 3. 云南省中医医院临床药理中心,云南昆明 650103
- 折叠
摘要
Abstract
Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.关键词
依折麦布片/生物等效性/安全性/药物代谢动力学/食物效应Key words
ezetimibe tablet/bioequivalence/safety/pharmacokinetics/food effect分类
医药卫生引用本文复制引用
赵沛月,兰静,梁文忠,张天财,张豫宁,李亚飞,赵守仁,贺建昌,董丽春,孙敏,胡艳君..依折麦布片在中国健康受试者中的生物等效性研究[J].中国临床药理学杂志,2024,40(16):2378-2382,5.
