卡培他滨片在肿瘤患者中的生物等效性研究  

Bioequivalence of capecitabine tablets in cancer patients

作　　者：徐国防[1] 高盼 刘平[1] 张孝磊[1] 荆萃[1] 张翠翠[1] 荆会霞 李晓苏[2] 齐琦 XU Guofang;GAO Pan;LIU Ping;ZHANG Xiaolei;JING Cui;ZHANG Cuicui;JING Huixia;LI Xiaosu;QI Qi(People's Hospital of Zhengzhou,Zhengzhou 450003,Henan,China;Henan Provincial People's Hospital,Zhengzhou 450000,Henan,China;School of Medicine,Jinan University,Guangzhou 510632,Guangdong,China)

机构地区：[1]郑州人民医院,河南郑州450003 [2]河南省人民医院,河南郑州450000 [3]暨南大学基础医学院,广东广州510632

出　　处：《中国临床药理学与治疗学》2020年第10期1119-1124,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金面上项目(81973341);广州市科技计划项目(202002030010)。

摘　　要：目的:研究卡培他滨片受试制剂与参比制剂在肿瘤患者中餐后单剂量给药后的药物代谢、生物等效性及安全性。方法:采用单剂量、随机、开放、双周期自身交叉研究设计。肿瘤患者口服卡培他滨片受试制剂或参比制剂0.6 g后,多点采集血样,HPLC-MS/MS法测定口服给药后血浆中卡培他滨及活性代谢产物5-氟尿嘧啶(5-FU)的血药浓度。Phoenix Win Nonlin7.0软件分析卡培他滨及5-FU的药动学参数,对受试制剂及参比制剂的生物等效性进行系统性评价。结果:受试制剂和参比制剂在肿瘤患者体内药物代谢动力学参数相近。参比制剂和受试制剂药物代谢动力学参数(Cmax,tmax,AUC0-t和AUC0-∞)分析表明,卡培他滨Cmax、AUC0-t及AUC0-∞的几何均值比值的90%置信区间分别为84.48~106.7、93.03~96.54和96.34~102.8。5-FU Cmax、AUC0-t及AUC0-∞的几何均值比值的90%置信区间分别为84.32~99.67,90.55~98.76和96.99~103.48,均在生物等效性范围(80.00%~125.0%)之内,且无严重不良事件发生。结论:现有研究对象结果显示,肿瘤患者口服卡培他滨片受试制剂和参比制剂具有良好的生物等效性。AIM:To evaluate the pharmacokinetics,bioequivalence,and safety of capecitabine tablet in cancer patients following single oral administration.METHODS:Based on an open-randomized two-period crossover designation,subjects were orally given capecitabine tablet(test or reference products,0.6 g single dosage).Blood samples were then collected and the plasma concentrations of capecitabine and its active metabolite,5-fluorouracil(5-FU)were examined by HPLC-MS/MS.The bioequivalence between the test and reference formulations were evaluated with the pharmacokinetic parameters determined by the Phoenix Win Nonlin 7.0software.RESULTS:The numbers of the major pharmacokinetic parameters in patients treated with test and reference products were similar.To analyze the numbers of Cmax,tmax,AUC0-t,AUC0-∞,the90%confidence interval(CI)for Cmax,AUC0-tand AUC0-∞were 84.48-106.70,93.03-96.54 and96.34-102.84,respectively.For the 5-FU,the90%CI of the for Cmax,AUC0-tand AUC0-∞were84.32-99.67,90.55-98.76 and 96.99-103.48,respectively.Both sets of numbers fell within the bioequivalent limit ranges of 80.00%-125.00%.No serious adverse event was observed.CONCLUSION:The current data indicate that the test and reference formulations of capecitabine tablets were bioequivalent in cancer patients.

关 键 词：卡培他滨 5-氟尿嘧啶 药物代谢动力学 生物等效性 

分 类 号：R969[医药卫生—药理学]