格列齐特缓释片人体药动学及生物等效性研究  

Study on Pharmacokinetics and Bioequivalence of Gliclazide Sustained-release Tablets in Healthy Volunteers

作　　者：冯泽岸[1,2] 巩慧敏[1,2] 张冬慧[1,2] 梁莉[1] 王婷[1] 乔华[1] 常威[1] 李丹[1] 苏曼 

机构地区：[1]兰州大学第一医院药剂科,兰州730000 [2]兰州大学药学院 [3]山东龙山制药有限公司

出　　处：《中国药师》2011年第9期1290-1293,共4页China Pharmacist

摘　　要：目的:建立测定人体血浆中格列齐特浓度的高效液相色谱法,研究格列齐特缓释片的人体药动学及生物等效性方法:20名男性健康志愿者进行随机双交叉试验,分别单剂量和多剂量口服格列齐特缓释片受试制剂和参比制剂,用高效液相色谱法测定人血浆中格列齐特血药浓度,用DAS2.1.1计算药动学参数,并评价两制剂的生物等效性。结果:在选定的色谱条件下格列齐特与内标及血浆杂质分离良好,在0.063～5μg·ml^(-1)范围内线性关系良好,提取回收率>77%,日内和日间精密度RSD均<15%。单剂量时受试制剂和参比制剂的体内药动学参数如下:t_(1/2)分别为(15.30±3.84)和(14.11±3.12)h、C_(max)分别为(2.34±0.72)和(2.19±0.80)μg·ml^(-1)、t_(max)分别为(5.60±1.23)和(6.45±1.54)h、AUC_(0～60)分别为(47.05±12.52)和(47.86±13.11)μg·h·ml^(-1)。受试制剂的相对生物利用度为(100.20±20.70)%,多剂量达稳态时受试制剂和参比制剂的体内药动学参数如下:t_(1/2)分别为(14.40±2.96)和(13.93±3.47)h、C_(max)分别为(2.86±0.93)和(2.85±1.45)μg·ml^(-1)、t_(mxa)分别为(4.85±1.63)和(4.30±1.72)h、AUC_(SS)分别为(42.44±12.97)和(44.18±19.99)μg·h·ml^(-1)、Cav分别为(1.77±0.54)和(1.84±0.83)μg·ml^(-1)、DF分别为(104.83±40.05)和(97.75±27.03)%。受试制剂的相对生物利用度为(104.00±33.40)%。结论:用HPLC法测定血浆中格列齐特浓度操作简单,结果准确,重复性好。两制剂在健康人体中具有生物等效性。Objective： To develop an HPLC method for the determination of gliclazide in human plasma and to investigate the pharmaeokinetics and bioequivalence of gliclazide sustained-release tablets in healthy volunteers. Method： An open randomized crossover study in 20 healthy male volunteers was carried out in single-dose or multiple-dose of the test and reference tablets. The concentrations of glielazide in plasma were determined by HPLC. The pharmaeokinetic parameters and bioequivalenee were statistically calculated with DAS2. 1.1 software. Result： The calibration curve was linear within the range from 0. 063 μg·ml^-1 to 5 μg·ml^-1 . The extraction recovery was above 77%. The intra-and inter-day RSDs were less than 15%. The main pharmacokinetic parameters of the test and reference preparations after a single dose were：t1/2 of （15.31 ±3.84） and （ 14. 11 ± 3.12） h,tmax of （5.60 ± 1.23） and （6. 45 ± 1.54） h,Cmax of （2. 34 ±0. 72） and （2. 19 ±0. 81 ） μg·ml^-1h,AUC0-60 of （47. 05 ± 12. 52） and （47.86 ± 13. 11 ）μg·h·ml^-1 ,respectively. The correlative bioavailability of the test preparation was （ 100. 20 ± 20. 70 ） %. The main pharmaeokinetie parameters of the test and reference preparations after multiple doses under stable condition were ： t1/2 was （ 14. 40 ± 2. 96 ） and （ 13.93 ± 3.47 ） h, C was （2.86±0.93） and （2.85±1.45） μg·ml^-1,tmax was （4.85 ±1.63） and （4.30±1.72） h,AUCss was （42.44±12.97） and （44.18±19.99） μg·h·ml^-1,Cav was （1.77 ±0.54） and （1.84±0.83） μg·ml^-1,DFwas （104.83±40.05） and （97.75± 27.03 ） %, respectively. The correlative bioavailability of the test preparation was （ 104. 00 ±33.40） %. Conclusion ： The HPLC method for the determination of gliclazide in plasma is proved to be convenient, accurate and reproducible. The two formulations are bioequivalent in healthy volunteers.

关 键 词：格列齐特缓释片 生物等效性 药动学 高效液相色谱法 

分 类 号：R969.1[医药卫生—药理学]