瑞格列奈片在中国健康志愿者中的药代动力学及生物等效性研究  

Pharmacokinetics and bioequivalence study of compound repaglinide tablets in healthy Chinese volunteers

作　　者：吴蔚 吉恋英 鲁萍 肖珍 张顺芝 程丽 宗利 WU Wei;JI Lian-ying;LU Ping;XIAO Zhen;ZHANG Shun-zhi;CHENG Li;ZONG Li(The First Hospital of Changsha,Changsha 410013,Hunan Province,China;Beijing Beilu Pharmaceutical Co.,Ltd,Beijing 100082,China)

机构地区：[1]长沙市第一医院药物Ⅰ期临床研究中心,湖南长沙410013 [2]北京北陆药业股份有限公司,北京100082

出　　处：《中国临床药理学杂志》2023年第2期266-270,共5页The Chinese Journal of Clinical Pharmacology

基　　金：湖南省卫生健康委科研计划项目资助项目(202113010356);湖南省自然科学基金资助项目(2021JJ80017);长沙市科技计划基金资助项目(kq2014007)。

摘　　要：目的 评价空腹和餐后给药条件下2种瑞格列奈片在健康受试者中生物等效性及安全性。方法 采用单中心、随机、开放、两周期(空腹试验)/四周期(餐后试验)、自身交叉的试验设计,空腹/餐后条件下分别入组34例和40例受试者,随机单次口服受试制剂和参比制剂1片(瑞格列奈片1.0 mg),采用LC-MS/MS法测定健康受试者血浆中瑞格列奈的药物浓度,采用WinNonlin软件进行药代动力学参数的计算,进行生物等效性评价。结果 受试者空腹单剂量口服受试制剂和参比制剂后,瑞格列奈的主要药动学参数Cmax分别为(7.67±3.94)和(7.55±4.32) ng·mL^(-1);AUC0-t分别为(23.11±8.72)和(23.59±8.97) h·ng·mL^(-1);AUC0-∞分别为(22.93±8.53)和(23.09±8.38) h·ng·mL^(-1);Tmax分别为1.00 h和0.75 h,餐后单剂量口服受试制剂和参比制剂后,瑞格列奈的主要药动学参数Cmax分别为(8.51±4.32)和(8.13±4.30) ng·mL^(-1);AUC0-t分别为(24.18±7.02)和(24.42±7.33) h·ng·mL^(-1);AUC0-∞分别为(24.89±7.49)和(25.08±7.50)h·ng·mL^(-1);Tmax分别为1.34 h和1.67 h,空腹试验和餐后试验的受试制剂与参比制剂Cmax、AUC0-t、AUC0-∞几何均值比的90%置信区间均落在80.00%~125.00%之间。结论 2种瑞格列奈片在中国健康成人受试者中具有生物等效性。Objective To evaluate the bioequivalence and safety of two kinds of repaglinide tablets in healthy subjects under fasting and postprandial conditions.Methods A single-center,randomized,open,two and four-cycle,self-crossover design was adopted.Thirty-four subjects were enrolled on fasting group and 40 subjects were enrolled on fed group.One test preparation and one reference preparation(repaglinide tablet,1.0 mg) were taken orally at random.The drug concentrations of repaglinide in plasma of healthy subjects were determined by LC-MS/MS,and the pharmacokinetic parameters were calculated by WinNonlin software.Results The main pharmacokinetic parameters of a single oral dose of repaglinide 1.0 mg under fasting condition for test and reference were as follows:Cmaxwere (7.67±3.94)and (7.55±4.32) ng·m L-1;AUC0-twere (23.11±8.72) and(23.59±8.97) h·ng·m L-1;AUC0-∞were (22.93±8.53) and(23.09±8.38) h·ng·m L-1;Tmaxwere 1.00 h and 0.75 h.The main pharmacokinetic parameters of a single oral dose of repaglinide 1.0 mg under fed condition for test and reference were as follows:Cmaxwere (8.51±4.32) and (8.13±4.30) ng·m L-1;AUC0-twere (24.18±7.02) and(24.42±7.33) h·ng·m L-1;AUC0-∞were (24.89±7.49) and (25.08±7.50) h·ng·m L-1;Tmaxwere 1.34and 1.67 h.The 90%confidence intervals of Cmax,AUC0-t,AUC0-∞geometric mean ratio between the test preparation and the reference preparation were all in the range of 80.00%-125.00%.Conclusion Two kinds of repaglinide tablets are bioequivalent in Chinese healthy volunteers.

关 键 词：瑞格列奈 生物等效 高变异药物 药代动力学 胰岛素促泌剂 健康志愿者 

分 类 号：R97[医药卫生—药品]