正葡萄糖钳夹技术评价人胰岛素注射液在中国健康受试者的药动学和药效学临床研究  

Evaluation of the pharmacokinetic and pharmacodynamic similarity of recombinant human insulin in healthy Chinese volunteers by euglycemic clamp technology

作　　者：张茜[1] 杨晶晶[1] 吴娟 章钦 秦慧玲 于亮 杜益君[3] 胡伟[1] ZHANG Qian;YANG Jingjing;WU Juan;ZHANG Qin;QIN Huiling;YU Liang;DU Yijun;HUWei(Drug Clinical Trial Research Center,The Second Hospital of Anhui Medical University,Hefei 230061,Anhui,China;Ningbo Kunpeng Biotechnology Co.LTD,Yuyao 315475,Zhejiang,China;Department of Endocrinology,The Second Hospital of Anhui Medical University,Hefei 230061,Anhui,China)

机构地区：[1]安徽医科大学第二附属医院药物临床试验研究中心,安徽合肥230061 [2]宁波鲲鹏生物科技有限公司,浙江余姚315475 [3]安徽医科大学第二附属医院内分泌科,安徽合肥230061

出　　处：《中国临床药理学与治疗学》2025年第3期385-391,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省转化医学研究院科研基金重点项目(2021zhyx-B14)。

摘　　要：目的:采用正葡萄糖钳夹技术,评价两种重组人胰岛素注射制剂在健康男性受试者中单次皮下注射的药代动力学(PK)、药效动力学(PD)相似性。方法:采用随机、开放、单剂量、双交叉两周期的试验设计,共招募24例健康男性受试者,随机分为两组,按照交叉给药方案每周期皮下注射0.2U/kg研究药物,采用正葡萄糖钳夹技术进行14h钳夹试验,进行药代动力学、药效动力学评价。结果:成功建立正葡萄糖钳夹技术,给药前及给药后各时间点检测的C肽水平提示,给药后两组受试者内源性胰岛素的分泌处于抑制状态,受试制剂和参比制剂在空腹条件下的C_(max)和AUC_(0-t)的几何均值比及其90%置信区间均在80.00%~125.00%范围内。结论:由宁波鲲鹏生物科技有限公司生产的人胰岛素注射液与参比制剂优泌林®在药动学及药效学方面具有相似性。AIM:To evaluate the pharmacokinetics(PK)and pharmacodynamics(PD)of two recombinant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We conducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investigational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.Cpeptide levels detected at each time point before and after administration indicated that endogenous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of C_(max) and AUC_(0-t) and 90%confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00%-125.00%.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin®in PK and PD characteristics in healthy Chinese subjects.

关 键 词：正葡萄糖钳夹 药代动力学 药效动力学 相似性 

分 类 号：R969[医药卫生—药理学]