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)

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。

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

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 singledose and multiple-dose administration. The plasmadrug 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 tmax, (13.4 ±1.2) h and (13.7 +1.3) h for t1/2, (2.4 +0.8) mg ·L-1and (2.3 ±0.6) mg· L-1 forcmax, (48 ±14)mg · h · L-1 and (48 +14) mg· h · L-1 forAUC0-60,(51+15) mg· h· L-1 and (50±14) mg· h· L-1for AUC0-∞, (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 tmax, (4.6±0.9) mg· L-1 and (4.7±1.1) mg· L-1 for cmax, (0.23 ±0.08) mg ·L-1and (0.26±0.08) mg· L-1 forcmin, (1.6±0.3) mg·L-1 and (1.6±0.3) mg · L-1 for mean value of steady plasma-drug concentration (cav),(94±19) mg· h · L-1 and (95 ±20) mg · h · L-1forAUCss, (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.