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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 establish a high performance liquid chromatographic method for the determination of gliclazide in human plasma and to study the pharmacokinetics and bioequivalence of Gliclazide Sustained-release Tablets: 20 male healthy volunteers were randomized, double-crossover , Respectively, single and multiple doses of oral gliclazide sustained-release tablets of the test preparation and reference preparation, high performance liquid chromatography determination of human plasma gliclazide plasma concentration, using the DAS2.1.1 pharmacokinetic parameters , And evaluate the bioequivalence of the two formulations. Results: Gliclazide was separated from internal standard and plasma impurities under the selected chromatographic conditions. The linearity was good in the range of 0.063 ~ 5μg · ml ~ (-1) and the recovery rate was> 77%. The intra- and inter-day Precision RSD <15%. The in vivo pharmacokinetic parameters of test and reference preparations were as follows: t_ (1/2) = (15.30 ± 3.84) and (14.11 ± 3.12) h and C_max = (2.34 ± 0.72) And (2.19 ± 0.80) μg · ml -1, t max were (5.60 ± 1.23) and (6.45 ± 1.54) h and AUC 0-60 were 47.05 ± 12.52 and 47.86 respectively ± 13.11) μg · h · ml -1. The relative bioavailability of the test preparations was (100.20 ± 20.70)%. The in vivo pharmacokinetic parameters of test preparations and reference preparations were as follows: t_ (1/2) = (14.40 ± 2.96) (2.86 ± 0.93) and (2.85 ± 1.45) μg · ml -1, respectively, and (mt) were (4.85 ± 1.63) and (4.30 ± 1.72 ) h and AUC_ (SS) were (42.44 ± 12.97) and (44.18 ± 19.99) μg · h · ml -1, respectively, and were 1.77 ± 0.54 and 1.84 ± 0.83 μg · ml -1 -1) and DF were (104.83 ± 40.05) and (97.75 ± 27.03)%, respectively. The relative bioavailability of the test preparation was (104.00 ± 33.40)%. Conclusion: HPLC method for the determination of plasma gliclazide concentration is simple, accurate and reproducible. Both formulations are bioequivalent in healthy humans.