克拉霉素对家兔体内格列吡嗪药动学特征的影响

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t₁/2_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t₁/2ke、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t₁/2ke、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。

Effect of clarithromycin on the pharmacokinetics of glipizide in rabbits

AIM To study the influence of clarithromycin on the pharmacokinetics of glipizide in healthy and diabetic rabbits. METHODS Glipizide （5 mg） was taken orally once to every rabbit. After 2 weeks of clearing stage, clarithromycin （0.25 g） was administered daily by intrapefitoneal injection bid for 3 d, then glipizide was taken orally at the same dosage on the fourth day. The blood was drawn from ear vein at 0.5, 1.5, 3, 5, 7, 9, 11, 24 and 35 h after administering glipizide in every rabbit. Then the blood concentration of glipizide was measured by HPLC. The pharmacokinetic parameter was calculated by 31x）7 software . The pharmacokinetics of glipizide in rabbits administered with or with- out clarithromycin were analyzed by auto-control. RESULTS The concentration time-curves were fit to the one-compart- ment model. In healthy rabbits administered with glipizide, the t1/2ke,pmax and AUC values were （3.99 ± 1.52）h, （4.05 ± 0.89）mg·L^-1 and （68.54 ± 15.67）mmg·L^-1 ,respectively. In healthy rabbits administered with glipizide and clarithromycin, the t1/2ke, pmax and AUC values were（4.26 ± 1.29）h,（5.41 ± 1.64）mg·L^-1 and （74.25± 18.94） mg·L^-1, respectively. In diabetic rabbits administered with glipizide, the t1/2ke, pmax and AUC values were （3.81 ± 0.89 ） h, （4.19 ± 1.25） mg·L^-1, （70.24 ± 13.21 ） mg·h·L^-1, respectively. In diabetic rabbits administered with glipizide and clarithromycin, the t1/2ke, Pmax, and AUC values were （4.28 ± 0.91）h, （5.31 ± 1.47）mg·L^-1 and （79.48 ± 17.69） mg·h· L^-1 respectively. There were notable differences on t1/zke, pamx,, AUG values of glipizide in rabbits admin- istered with or without clarithromycin. CONCLUSION Clarithromycin shows significant inhibition on the pharmacokinet- ics of glipizide.