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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。
OBJECTIVE: To compare human pharmacokinetics and relative bioavailability of domestic and imported gliclazide extended-release tablets. Methods: The plasma concentrations of gliclazide in 20 healthy male volunteers were determined by liquid chromatography-mass spectrometry (LC-MS / MS) in single-and double-dose 4-cycle double crossover design. Results: After a single oral administration of gliclazide sustained-release tablets, the pharmacokinetic parameters were as follows: tmax was (7.2 ± s1.5) h and (6.9 ± 1.4) h, cmax was (2.4 ± 0.8) mg (13.4 ± 1.2) h and (13.7 ± 1.3) h, and AUC0 ~ 60 (48 ± 14) mg · h · L-1 for L-1 and 2.3 ± 0.6 mg · L- (51 ± 15) mg · h · L-1 and (50 ± 14) mg · h · L-1, (48 ± 14) mg · h · L-1 and mean residence time (MRT) (22.4 ± 1.9) h and (22.78 ± 1.9) h. The steady-state pharmacokinetic parameters of domestic and imported gliclazide sustained-release tablets were (6.1 ± 1.4) h and (6.5 ± 1.4) h and (4.6 ± (0.23 ± 0.08) mg · L-1 and (0.26 ± 0.08) mg · L-1, respectively, with a mean steady-state plasma concentration of (1.6 ± 0.3) mg · L-1 and (1.6 ± 0.3) mg · L-1 for caval cavations and (94 ± 19) mg · h-1 and (95 ± 20) mg · h- -1 and (282 ± 33)% and (283 ± 43)% respectively. The relative bioavailabilities of both domestic and imported gliclazide sustained-release tablets were (102 ± 9)% and (99 ± 10)%, respectively. Pharmacokinetic parameters of the above single and multiple administrations showed no significant difference by ANOVA (P> 0.05). Conclusion: Two-sided one-tailed t-test showed that the two preparations were bioequivalent.