格列齐特2种缓释片单次和多次给药 的药动学和生物利用度比较(英文)  

Pharmacokinetics and bioavailability of two kinds of gliclazide sustained-release tablets following a single and multiple dose in healthy volunteers

作　　者：邹健军[1] 肖大伟[1] 朱余兵[1] 莫陵[1] 于翠霞[1] 顾荣[1] 胡云芳[1] 钱薇[1] 娄晟[1] 

机构地区：[1]南京医科大学附属南京第一医院国家药品临床研究基地,江苏南京210006

出　　处：《中国新药与临床杂志》2005年第5期337-341,共5页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的:比较国产和进口格列齐特缓释片的人体药动学和相对生物利用度。方法:采用单次和多次给药的4周期双交叉设计,用液相色谱质谱联用法测定20名健康男性志愿者血浆中格列齐特的浓度。结果:单次口服国产和进口格列齐特缓释片后的药动学参数分别为:tmax为(7.2±s1.5)h和(6.9±1.4)h,cmax为(2.4±0.8)mg·L-1和(2.3±0.6)mg·L-1,t1/2为(13.4±1.2)h和(13.7±1.3)h,AUC0～60为(48±14)mg·h·L-1 和(48±14)mg·h·L-1,AUC0～∞为(51±15)mg·h·L-1和(50±14)mg·h·L-1,平均滞留时间(MRT)为(22.4±1.9)h和(22.78±1.9)h。多次(60mg,6d)口服国产和进口格列齐特缓释片后的稳态药动学参数分别为:tmax为(6.1±1.4)h和(6.5±1.4)h,cmax为(4.6±0.9)mg·L-1和(4.7±1.1) mg·L-1,cmin为(0.23±0.08)mg·L-1和(0.26±0.08)mg·L-1,稳态血药浓度均值(cav)为(1.6±0.3)mg·L-1和(1.6±0.3)mg·L-1,AUCss为(94±19)mg·h·L-1和(95±20)mg·h·L-1,波动度(DF)为(282±33)%和(283±43)%。单次和多次口服国产与进口格列齐特缓释片相对生物利用度分别为(102±9)%和(99±10)%。上述单次和多次给药的药动学参数经方差分析无显著差异(P>0.05)。结论:双单侧t检验表明2种制剂具有生物等效性。AIM: To compare the pharmacokinetics and relative bioavailability of the domestic and imported sustained-release tablets of gliclazide in healthy volunteers. METHODS:The study was performed by an four-period crossover design with single-dose and multiple-dose administration. The plasma-drug concentrations of twenty male healthy volunteers were determined by liquid chromatography with mass spectrum detector method (LC-MS). RESULTS: The pharmacokinetic parameters after a single oral dose of the domestic and imported gliclazide tablets were ((7.2)±s 1.5) h and (6.9±1.4) h for t_(max), (13.4±(1.2) h) and (13.7±1.3) h for t_(1/2), (2.4±0.8) (mg·)L^(-1) and (2.3±0.6) mg·L^(-1) for c_(max), (48±14) (mg·)(h·L^(-1)) and (48±14) mg·(h·L^(-1)) for AUC_(0-60), (51±15) mg·h·L^(-1) and (50±14) mg·h·L^(-1) for AUC_(0-∞), (22.4±1.9) h and (22.8±1.9)h for MRT, respectively. The steady state pharmacokinetic parameters after multiple doses of the domestic and imported gliclazide tablets were (6.1±(1.4) h) and ((6.5±)1.4) h for t_(max), (4.6±0.9) mg·L^(-1) and ((4.7±1.1)) mg·L^(-1) for c_(max), (0.23±(0.08)) mg·L^(-1) and (0.26±0.08) mg·L^(-1) for c_(min), (1.6±(0.3)) mg·L^(-1) and (1.6±0.3) mg·L^(-1) for mean value of steady plasma-drug concentration (c_(av)), ((94±)19) mg·h·L^(-1) and (95±20) mg·h·L^(-1) for AUC_(ss), (282±33)% and (283±43)% for degree of fluctuation (DF), respectively. The relative bioavailability of the domestic gliclazide tablet to the imported gliclazide tablet following a single and multiple dose were (102±9)% and (99±10)%, respectively. Main pharmacokinetic parameters between the two formulations in both single and multiples dose studies showed no statistical difference (P>0.05). CONCLUSION: The result of two one side t-test shows that the two formulations are bioequivalent.

关 键 词：格列齐特 迟效制剂 色谱法 高压液相 光谱分析 质量 药动学 生物利用度 

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