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目的研究克拉霉素在健康和糖尿病家兔体内对格列吡嗪片代谢的影响。方法健康新西兰家兔和实验性糖尿病家兔各5只,每只口服格列吡嗪5 mg,经2周清洗期后,每只家兔予克拉霉素0.25 g,ig,bid,持续3 d,第4天口服相同剂量格列吡嚎。在给予格列吡嗪前及给药后O.5、1.5、3、5、7、9、11、24、35 h,经耳缘静脉采血,用HPLC法测定各点格列吡嗪的血药浓度,用3P97数据处理软件计算药动学参数。采用自身对照法分析给予克拉霉素前后格列吡嗪药动学的变化。结果正常组家兔单用格列吡嗪,其t_1/2_(ke)、ρ_(max)、AUC分别为(3.99±1.52)h、(4.05±0.89)mg·L~(-1)、(68.54±15.67)mg.h·L~(-1),加用克拉霉素后又分别为(4.26±1.29)h、(5.41±1.64)mg·L~(-1)、(74.25±18.94)rag·h·L~(-1)。糖尿病组家兔单用格列毗嗪,其t_1/2ke、ρ_(max)、AUC分别为(3.81±0.89)h、(4.19±1.25)mg·L~(-1)、(70.24±13.21)mg·h·L~(-1),加用克拉霉素后又分别为(4.28±O.91)h、(5.31±1.47)mg·L~(-1)、(79.48±17.69)mg·h·L~(-1)。给予克拉霉素前后格列吡嗪的t_1/2ke、ρ_(max)、AUC差异均存有统计学意义(P<0.5)。结论克拉霉素对家兔体内格列吡嗪的药动学有明显的影响。
Objective To study the effect of clarithromycin on the metabolism of glipizide tablets in healthy and diabetic rabbits. Methods Five healthy New Zealand rabbits and experimental diabetic rabbits were given 5 mg glipizide orally, and each rabbits were given clarithromycin 0.25 g, ig, bid for 3 days after 2 weeks of cleaning. On the fourth day, the same dose of glibenclamide orally. Before administration of glipizide and O.5,1.5,3.5,7,9,11,24,35 h after administration, the blood was collected via the ear vein and the glipizide blood at each point was determined by HPLC Drug concentration, using 3P97 data processing software to calculate pharmacokinetic parameters. The pharmacokinetics of glipizide before and after the administration of clarithromycin was analyzed by self-control method. Results In normal rabbits, the t 1/2 ke, p max and AUC were (3.99 ± 1.52) h, (4.05 ± 0.89) mg · L -1, (4.26 ± 1.29) h, (5.41 ± 1.64) mg · L -1, (74.25 ± 18.94) mg · L -1, respectively) after treatment with clarithromycin, rag · h · L ~ (-1). In the diabetic group, the plasma levels of t 1 / 2ke, ρ max and AUC were (3.81 ± 0.89) h, (4.19 ± 1.25) mg · L -1, (70.24 ± 13.21) (4.28 ± 0.91) h, (5.31 ± 1.47) mg · L -1, (79.48 ± 17.69) mg ··L -1, respectively after treated with clarithromycin h · L ~ (-1). Before and after giving clarithromycin glipizide t_1 / 2ke, ρ_ (max), AUC differences were statistically significant (P <0.5). Conclusion Clarithromycin has significant effect on the pharmacokinetics of glipizide in rabbits.