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目的:研究复方盐酸二甲双胍片在健康志愿者体内的药物动力学和生物等效性。方法:18名男性健康志愿者随机交叉单次口服复方盐酸二甲双胍片(含盐酸二甲双胍1000 mg,格列本脲5 mg,受试制剂)或联合服用盐酸二甲双胍片1 000 mg和格列本脲片5 mg(参比制剂)后,采用HPLC法分别测定盐酸二甲双胍和格列本脲的经时血药浓度,用3P97软件计算其药物动力学参数和相对生物利用度,评价两种制剂的生物等效性。结果:单次口服受试制剂和参比制剂后,盐酸二甲双胍主要药物动力学参数C_(max)分别为(1.60±0.55)μg·ml~(-1)和(1.46±0.46)μg·ml~(-1),t_(max)分别为(2.1±0.7)h和(2.5±0.8)h,t_(1/2)分别为(4.9±1.7)h和(4.3±1.6)h,AUC_(0→24)分别为(10.47±2.89)μg·ml~(-1)·h和(9.22±2.56)μg·ml~(-1)·h,AUC_(0→∞)分别为(10.95±3.13)μ·ml~(-1)·h和(9.53±2.73)μg·ml~(-1)·h,受试制剂的相对生物利用度F_(0→24)为114.8%±17.6%。格列本脲主要药物动力学参数C_(max)分别为(117.70±28.38)μg·L~(-1)和(106.92±33.76)μg·L~(-1),t_(max)分别为(4.1±2.7)h和(3.8±1.8) h,t_(1/2)分别为(7.6±4.1)h和(8.8±3.9)h,AUC_(0→30)分别为(899.97±296.76)μg·L~(-1)·h和(902.64±353.82)μg·L~(-1)·h,AUC_(0→∞)分别为(943.00±290.09)μg·L~(-1)·h和(989.82±399.90)μg·L~(-1)·h,受试制剂的相对生物利用度F_(0→30)为104.91%±28.31%。结论:两制剂两组分的AUC、C_(max)对数值,经F分析、双单侧t检验和(1-2α)%置信区间法统计分析。表明两种制剂具有生物等效性。
Objective: To study the pharmacokinetics and bioequivalence of compound metformin hydrochloride tablets in healthy volunteers. Methods: Eighteen healthy volunteers were randomized to receive oral metformin hydrochloride (containing metformin hydrochloride 1000 mg, glyburide 5 mg, test preparation) or a combination of metformin HCl 1000 mg and glibenclamide tablets After 5 mg (reference preparation), the plasma concentrations of metformin hydrochloride and glyburide were determined by HPLC. The pharmacokinetic parameters and relative bioavailability were calculated by 3P97 software. The bioavailability of the two preparations was evaluated Validity. Results: The main pharmacokinetic parameters of metformin hydrochloride were (1.60 ± 0.55) μg · ml -1 and (1.46 ± 0.46) μg · ml -1, respectively after single oral administration of the test preparation and reference preparation. (-1) and t (max) were (2.1 ± 0.7) h and (2.5 ± 0.8) h and (t 1/2) were 4.9 ± 1.7 and 4.3 ± 1.6 h, (10.47 ± 2.89) μg · ml -1 · h and (9.22 ± 2.56) μg · ml -1 · h, respectively, and the AUC_ (0 → ∞) were (10.95 ± 3.13) The relative bioavailability of the tested preparation was 114.8% ± 17.6%. The relative bioavailability of the tested preparation was 114.8% ± 17.6%. The main pharmacokinetic parameters of glibenclamide C_ (max) were (117.70 ± 28.38) μg · L -1 and (106.92 ± 33.76) μg · L -1, respectively, and t max were (7.6 ± 4.1) h and (8.8 ± 3.9) h respectively, and the AUC_ (0 → 30) were (4.1 ± 2.7) h and (3.8 ± 1.8) h and (t 1/2) were respectively 899.97 ± 296.76 μg · (-1) · h and (902.64 ± 353.82) μg · L -1 · h -1 respectively, and the AUC 0 ~ ∞ were (943.00 ± 290.09) μg · L -1 · h and 989.82 ± 399.90) μg · L -1 · h, the relative bioavailability of the test preparation was F (0 → 30) was 104.91% ± 28.31%. Conclusion: The AUC and C max logarithm of the two components of the two preparations were statistically analyzed by F-analysis, double unilateral t-test and (1-2α)% confidence interval method. Both formulations were shown to be bioequivalent.