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

目的:研究格列齐特缓释片的药动学及相对生物利用度,验证国产与进口格列齐特缓释片的生物等效性。方法:采用拉丁方试验设计,研究受试者在空腹条件下分别单剂量和多剂量口服格列齐特缓释片后,采用高效液相色谱法测定人血浆中格列齐特的浓度,计算其药动学参数和相对生物利用度,评价2制剂的生物等效性。结果:单剂量口服格列齐特缓释片受试制剂(国产)和参比制剂(进口)的主要药动学参数分别为:tma(x6.71±1.43)、(7.38±1.50)h,Cma(x0.813±0.178)、(0.782±0.129)μg.mL-1,AUC0～7(221.29±5.86)、(21.09±5.34)μg.h.mL-1,AUC0～∞(23.19±7.49)、(23.15±5.64)μg.h.mL-1,t1/2k(e18.79±5.24)、(20.03±5.67)h;多剂量口服格列齐特缓释片达稳态后2制剂主要药动学参数分别为:AUCs(s27.85±9.77)、(27.63±10.84)μg.h.mL-1,Cssmax(1.892±0.503)、(1.829±0.521)μg.mL-1,tssma(x5.33±1.24)、(6.13±1.42)h,Cssmi(n0.771±0.379)、(0.830±0.478)μg.mL-1,血药浓度波动度DF(103.8±40.0)%、(97.6±52.9)%。结论:2制剂具有生物等效性。

OBJECTIVE：To study the pharmacokinetics and relative bioavailability of Gliclazide sustained-release tablets,and to validate the bioequivalence between the domestic and the imported Gliclazide sustained-release tablets.METHODS：In Latin square experiment,32 healthy volunteers were given single and multiple oral-dose of Gliclazide sustained-release tablet in foodless condition,and pharmacokinetics and bioequivalence of the two formulations were evaluated and the plasma concentrations were de-termined by HPLC.RESULTS：The main pharmacokinetic parameters of domestic preparation vs.imported preparation after singleoral-dose of Gliclazide sustained-release tablets were as followst：max（6.71±1.43）h vs.（7.38±1.50）h;Cmax（0.813±0.178）μg.mL-1vs.（0.782±0.129）μg.mL-1;AUC0～72（21.29±5.86）μg.h.mL-1 vs.（21.09±5.34）μg.h.mL-1;AUC0～∞（23.19±7.49）μg.h.mL-1vs.（23.15±5.64）μg.h.mL-1;t1/2ke（18.79±5.24）h vs.（20.03±5.67）h.The main steady state pharmacokinetic parameters of do-mestic preparation vs.imported preparation after the multiple-dose of Gliclazide sustained-release tablets were as follows：AUCss（27.85±9.77）μg.h.mL-1 vs.（27.63±10.84）μg.h.mL-1;Cssmax（1.892±0.503）μg.mL-1 vs.（1.829±0.521）μg.mL-1;tssmax（5.33±1.24）h vs.（6.13±1.42）h;Cssmin（0.771±0.379）μg.mL-1 vs.（0.830±0.478）μg.mL-1;DF：（103.8±40.0）% vs.（97.6±52.9）%.CONCLUSION：The two preparations are bioequivalent.