国产盐酸二甲双胍缓释片的人体药动学及相对生物利用度  

Pharmacokinetic and relative bioavailability of domestic metformin HCI extended release tablets

作　　者：汤琤[1] 钟国平[1] 刘伟东[1] 王雪丁[1] 曾桂雄[1] 黄丽慧[1] 黄民[1] 廖晓星[1] 

机构地区：[1]中山大学药学院临床药理研究所,广州510080

出　　处：《中国新药杂志》2005年第2期197-200,共4页Chinese Journal of New Drugs

摘　　要：目的:研究健康志愿者单次及多次口服国产盐酸二甲双胍缓释片的药动学及与进口制剂比较的相对生物利用度。方法:40例健康志愿者随机交叉自身对照分别口服国产及进口盐酸二甲双胍缓释片,单剂量1g及多剂量1q,qd,5d。用HPLC法检测服药后0～24h(单剂量)和0～120h(多剂量)内系列时间点的血药浓度,以外标法定量。结果:20例志愿者单次口服国产和进口制剂1g后,C_(max)分别为(1893.3±533.8)及(1800.6±512.9)μg·L^(-1);T_(max)分别为(3.6±0.7)及(3.4±0.7)h;t_(1/2)分别为(6.2±1.7)及(6.3±1.7)h;AUC_(0～24)分别为(12582.8±4030.2)及(11179.2±2156.7)μg·L^(-1)·h。国产相对进口制剂的生物利用度(F)为(113.4±37.0)%。20例志愿者多次口服2种制剂1000mg·次^(-1)·d^(-1),5d后,C_(max)分别为(1536.3±385.0)及(1477.5±340.1)μg·L^(-1);T_(max)分别为(3.3±0.8)及(3.2±0.7)h;C_(max)分别为(68.3±23.7)及(77.5±21.3)μg·L^(-1);C_(av)分别为(412.7±91.6)及(418.1±95.3)μg·L^(-1);t_(1/2)分别为(7.7±2.1)及(7.6±2.1)h;AUC_(SS)分别为(9904.3±2199.2)及(10034.2±2286.0)μg·L^(-1)·h;波动度(DF)分别为(327.4±67.5)%及(303.8±57.7)%。国产相对进口制剂的F为(101.4±23.2)%。结论:两制剂具生物等效性。Objective: To evaluate the pharmacokinetics and relative bioavailability of metformin HC1 extended release tablets made in China (test) to metformin HC1 extended release tablets imported (reference). Methods: An open-label, randomized and crossover clinical trial recruited 40 healthy volunteers, who were equally randomized to give either a single oral dose (1g) or a multiple oral dose (1g·d^(-1)×5d) of reference and test metformin HC1. The plasma concentrations of metformin HC1 were measured in 24 hours post single dose and 120 hours post multiple doses, respectively, using RP-HPLC. Results: The pharmacokinetic parameters of test and reference metformin were as follows-single dose: C_(max)(1893.3±533.8)μg·L^(-1)vs. (1800.6±512.9)μg·L^(-1), T_(max)(3.6±0.7)vs. (3.4±0.7)h, t_(1/2)(6.2±1.7)vs. (6.3±1.7)h, AUC_(0-t)(12582.8±4030.2)vs. (11179.2±2156.7)μg·h·L^(-1). The relative bioavailability of test to reference metformin was (113.4±37.0)%; Multiple doses: C_(max)(1536.3±385.0)vs. (1477.5±340.1)μg·L^(-1), C_(min)(68.3±23.7)vs. (77.5±21.3)μg·L^(-1), T_(max)(3.3±0.8)vs. (3.2±0.7)h, t_(1/2)(7.7±2.1)vs. (7.6±2.1)h, AUC_(SS)(9904.3±2199.2)vs. (10034.2±2286.0)μg·h·L^(-1), C_(av)(412.7±91.6)vs. (418.1±95.3)μg·L^(-1), DF (327.4±67.5)% vs. (303.8±57.7)%. The relative bioavailability of test to reference preparation was (101.4±23.2)%. Conclusion: The reference metformin is bioequivalent to test metformin.

关 键 词：盐酸二甲双胍缓释片 高效液相色谱法 药动学 生物利用度 

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