替格瑞洛片健康人体生物等效性评价  

Study on bioequivalence of ticagrelor tablets in healthy subjects

作　　者：崔英子[1] 周艳楠 王鸯 杨海淼[1] CUI Ying-zi;ZHOU Yan-nan;WANG Yuan;YANG Hai-miao(Laboratory of Phase I Clinical Trials,the Affiliated Hospital to Changchun University of Chinese Traditional Medicine,Changchun 130021,China;Chiatai Tianqing Pharmaceutical Co.,Ltd.,Nanjing 210000,China)

机构地区：[1]长春中医药大学附属医院Ⅰ期临床试验研究室,长春130021 [2]正大天晴药业集团股份有限公司,南京210000

出　　处：《中国新药杂志》2020年第12期1397-1404,共8页Chinese Journal of New Drugs

摘　　要：目的:研究替格瑞洛片在健康人体的药动学特征,并对2种制剂的生物等效性和安全性进行评价。方法:空腹/餐后共48名健康受试者口服替格瑞洛片受试制剂和参比制剂,采用随机、开放、四周期、两交叉单次空腹/餐后状态自身对照的试验方法,用液相色谱-串联质谱法测定服药后48 h内15个不同时间点的血药浓度,计算主要药动学参数。采用方差分析,双单侧t检验和90%置信区间分析进行生物等效性评价。结果:空腹状态下,受试制剂与参比制剂替格瑞洛Cmax的几何均值比值的90%置信区间为95.02%~109.91%,活性代谢物AR-C124910XX的Cmax的几何均值比值的90%置信区间为92.94%~106.85%;替格瑞洛AUC0-t的几何均值比值的90%置信区间为98.59%~107.58%,AR-C124910XX的AUC0-t几何均值比值的90%置信区间为97.14%~104.84%,替格瑞洛AUC0-∞的几何均值比值的90%置信区间为98.42%~107.32%,AR-C124910XX的AUC0-∞几何均值比值的90%置信区间为97.97%~104.62%,均符合生物等效范围(80.00%~125.00%)要求。餐后状态下,受试制剂与参比制剂,替格瑞洛Cmax的几何均值比值的90%置信区间为95.62%~114.36%,AR-C124910XX的Cmax几何均值比值的90%置信区间为93.73%~108.74%;替格瑞洛AUC0-t的几何均值比值的90%置信区间为96.43%~102.93%,AR-C124910XX的AUC0-t几何均值比值的90%置信区间为95.32%~101.88%,替格瑞洛AUC0-∞的几何均值比值的90%置信区间为97.05%~102.76%,AR-C124910XX的AUC0-∞几何均值比值的90%置信区间为93.57%~101.03%,符合生物等效范围(80.00%~125.00%)要求。结论:在空腹和餐后条件下,替格瑞洛片受试制剂与参比制剂具有生物等效性。Objective:To evaluate the pharmacokinetic characteristics of ticagrelor tablets in healthy subjects and the bioequivalence and safety of two preparations.Methods:A total of 48 healthy subjects were given oral ticagrelor tablets and reference preparation(Brilinta■)in a randomized,open label,four-period,two-cross,single-dose fasting/postprandial self-control study.Plasma concentrations at 15 different time points within 48 h after drug administration were determined by LC-MS/MS,and the main pharmacokinetic parameters were calculated.The bioequivalence was evaluated by ANOVA,twin-sided t-test and 90%confidence interval analysis.Results:Under fasting state,the 90%confidence intervals of the geometric mean ratio of the Cmax,AUC0-t,and AUC0-∞of tegrilol and the active metabolite AR-C124910 xx of the tested and reference preparations were 95.02%~109.91%and 92.94~106.85%,98.59%~107.58%and 97.14%~104.84%,98.42%~107.32%and 97.97%~104.62%,respectively.Under postprandial state,the 90%confidence intervals of the geometric mean ratio of Cmax,AUC0-t,and AUC0-∞of ticagrelor and AR-C124910 xx were 95.62%~114.36%and 93.73%~108.74%,96.43%~102.93%and 95.32%~101.88%,97.05%~102.76%and 93.57%~101.03%,respectively.All of the parameters met the bioequivalence requirement(80.00%~125.00%).Conclusion:The test and reference ticagrelor tablets are bioequivalent under both fasting and postprandial state.

关 键 词：替格瑞洛片 液相色谱-串联质谱法 生物等效性 

分 类 号：R969[医药卫生—药理学]