国产与进口格列齐特缓释片人体生物等效性研究  

The bioequivalence study of domestic and imported gliclazide sustained release tablets

作　　者：田媛[1] 吴黎莉[2] 王源园[1] 李静[1] 周燕文[3] 张尊建[1] 

机构地区：[1]中国药科大学分析测试中心,药物质量与安全预警教育部重点实验室,南京210009 [2]中国医学科学院皮肤病研究所 [3]广西医科大学第一附属医院国家药品临床研究基地

出　　处：《中国糖尿病杂志》2009年第5期395-398,共4页Chinese Journal of Diabetes

摘　　要：目的评价格列齐特缓释片试验制剂和市售参比制剂的人体生物等效性。方法采用高效液相色谱-质谱联用技术,以内标法测定20名男性健康受试者单次和多次交叉给予格列齐特缓释片后的血药浓度经时过程,估算药代动力学参数。结果口服格列齐特缓释试验片(30mg)和参比片(30mg)后,受试及参比制剂中药物主要药代动力学参数如下:单次给药时达峰浓度(Cmax)分别为1.21±0.26μg/ml和1.09±0.24μg/ml,达峰时间(Tmax)分别为7.4±1.8h和7.0±1.6h,消除半衰期t1/2(Kel)分别为14.82±4.10h和13.57±4.16h,AUC0～72分别为26.23±8.65μg·h·ml-1和25.88±8.87μg·h·ml-1,AUC0～∞分别为27.65±9.80μg·h·ml-1和27.12±9.90μg·h·ml-1;多次给药时Cmax分别为1.37±0.49μg/ml和1.31±0.41μg/ml;谷浓度(Cmin)分别为0.069±0.075μg/ml和0.060±0.066μg/ml;平均稳态血药浓度(Cav)分别为0.41±0.20μg/ml和0.42±0.19μg/ml;Tmax分别为6.0±1.7h和6.6±2.6h;波动系数(DF)分别为3.46±0.99和3.29±1.06;稳态药时曲线下面积(AUCss)别为29.66±14.10μg·h·ml-1和29.95±13.40μg·h·ml-1。AUC和AUCss经对数转换后方差分析检验,差异无统计学意义。结论试验制剂和参比制剂生物等效。Objective To compare the bio-availability between test gliclazide sustained release tablet and commercially available reference tablet. Methods A HPLC/MS method was developed and used to determine gliclazide plasma concentrations of 20 healthy volunteers in an open randomized two-way crossover test after single oral dose and multiple oral doses. The pharmacokinetic parameters were estimated. Results After single oral gliclazide sustainde release tablets of reference （30mg） or test （30mg） drugs were given, gliclazide plasma concentration against time was calculated and evaluated. The main pharmacokinetic parameters after a single oral dose of test versus reference drug were as follows： Cmax was 1.21±0.26 vs 1.09±0. 24μg/ml, Tmax was 7.4±1.8 vs 7.0±1.6h, AUC0-72 was 26.23±8. 65 vs 25.88±8.87μg.h.ml^-1, respectively, AUC0-∞ was 27.65±9. 80 vs 27.12±9.90μg.h.ml^-1. The Crmax, Cmin Cav, Tmax, DF, AUC55 of gliclazide test versus reference tablets after multiple oral doses were 1.37±0. 49 vs 1.31±0. 41μg/ml; 0. 069±0. 075 vs 0. 060±0. 066μg/ml; 0. 41±0. 20 vs 0. 42±0.19μg/ml; 6.0±1.7 vs 6.6±2.6h;3.46±0.99 vs 3, 29±1.06; 29.66±14. 10 vs 29.95±13.40μg.h.ml^-1 respectively. The AUC and AUC and were tested after natural logarithmic transformation and no difference with statistical significance was found. Conclusions The test formulation is bioequivalent to the reference formulation for gliclazide.

关 键 词：格列齐特 缓释片 生物等效性 高效液相色谱-质谱联用 

分 类 号：R96[医药卫生—药理学]