国产重组人胰岛素生物等效性研究  

Bioequivalence study of domestic recombinant human insulin

作　　者：董艳[1,2] 曾勇[2] 慈小燕[2] 高晶[2] 武卫党[2] 李薇[2] 李亚卓[2] 魏滋鸿 伊秀林[2] 江立新 孙磊 周伟 

机构地区：[1]天津医科大学药学院,天津300070 [2]天津药物研究院有限公司释药技术与药代动力学国家重点实验室,天津300193 [3]合肥天麦生物科技发展有限公司,合肥230601

出　　处：《中国临床药理学杂志》2015年第18期1837-1839,共3页The Chinese Journal of Clinical Pharmacology

基　　金：国家重大新药创制科技重大专项基金资助项目(2012ZX09304002)

摘　　要：目的 评价国产与国外已上市的重组人胰岛素注射液在Beagle犬体内的药代动力学及生物等效性。方法 用两制剂、双周期、自身对照随机交叉单剂量实验设计。12只健康Beagle犬分为实验组（试验药）和对照组（对照药）,每组5只,皮下注射重组人胰岛素5 U,不同时间经静脉采集血浆,测定动物血糖水平;放射免疫分析（RIA）法检测血药浓度;用DAS 2.0软件拟合计算药代动力学参数,并进行生物等效性分析。结果 实验组和对照组胰岛素主要药代动力学参数：t1/2为（1.06±0.17）,（1.06±0.35）h;Cmax为（97.10±45.20）,（91.30±28.20）μU·m L-1;tmax为（0.49±0.19）,（0.49±0.18）h;AUC0-t为（168.00±40.50）,（168.00±41.90）μU·m L-1·h。血浆最低葡萄糖浓度（Cmin）分别为（1.36±0.28）,（1.37±0.34）mmol·L-1,最低浓度所需时间（tmin）分别为（1.57±0.55）,（1.74±0.65）h。Cmax和AUC0-t[1-2α]置信区间分别为85.5%~117.7%和97.0%~103.3%。结论 2种重组人胰岛素注射剂在健康Beagle犬体内具有生物等效性。Objective To investigate the pharmacokinetic and bit- equivalence of domestic and imported recombinant human insulin injec- tion in Beagle dogs. Methods Twelve Beagle dogs were assigned into two groups and the two groups were separately singlely given with test preparation and reference preparation in the same dose in sc injection method according to a randomized two - phase crossover. The plasmas were sampled at different time points after subcutaneous administration and the blood glucose levels were determined by Roche Glucose meter synchronously. The radioimmunoassay （RIA） method was used to deter- mine the concentration of blood insulin at the different sample points. The pharmacokinetic parameters were calculated by DAS 2. 0 software. Results The main pharmacokinetics parameters of test preparation and reference preparation were as follows： tl/2 were （1.06 ± 0. 17 ） and （1.06±0.35） h; Cmax were （97.10 ±45.20） and （91.30 ±28.20） μU mL-1; tmax were （0.49 ±0.19） and （0.49 ±0.18） h; area AUC0-t were （168.00±40.50） and （168.00 ±41.90） μU mL-1 h, respectively. What＇s more, Cmi. of the test and the referenc were （ 1.36 ± 0. 28 ） and （ 1.37 ± 0. 34 ） mmol L-1 separately, and the tmin were （1.57 ± 0.55） and （1.74 ± 0.65） h, respectively. The confidence intervals of Cmax and AUC0-t are 85.5% - 117.7% and 97. OVA, - 103.3%. Conclusion The results showed that the test and the reference preparation meet the regulatory criteria for the pharmacokinetic equivalence.

关 键 词：糖尿病 胰岛素 重组人胰岛素注射液 药代动力学 生物等效性 

分 类 号：R969.1[医药卫生—药理学] R977.15[医药卫生—药学]