罗红霉素对家兔体内格列吡嗪药动学的影响

目的:研究罗红霉素在健康和糖尿病家兔体内对格列吡嗪胶囊代谢的影响。方法:健康对照组家兔和糖尿病组家兔各5只,每只口服格列吡嗪5mg。经2周清洗期后,每只家兔口服罗红霉素50.0mg,每天2次,持续3天,第4天口服相同剂量格列吡嗪。所有家兔均在给予格列吡嗪前及给药后0.5、1.5、3、5、7、9、11、24、35h,经耳缘静脉采血,用HPLC法测定各时间点格列吡嗪的血药浓度,测得的血药浓度结果用药动学软件DAS 2.0进行曲线拟合,采用自身对照法分析给予罗红霉素前后格列吡嗪药动学的变化。结果:格列吡嗪在家兔体内的药动学符合单室模型,健康对照组家兔单用格列吡嗪,其t1/2、Cmax、AUC分别为(2.9±0.4)h,(5815±940)μg/L,(58919±860)μg.h.L-1;加用罗红霉素后其t1/2、Cmax、AUC分别为(3.5±0.9)h,(6165±764),(76515±1830)μg.h.L-1。糖尿病组家兔单用格列吡嗪,其t1/2、Cmax、AUC分别为(1.7±0.4)h,(4307±580)μg/L,(32469±786)μg.h.L-1;加用罗红霉素后其t1/2、Cmax、AUC分别为(3.2±1.5)h,(8531±1479)μg/L,(76489±1588)μg.h.L-1。给予罗红霉素前后格列吡嗪的t1/2、Cmax、AUC差异均存有统计学意义(P<0.05)。结论:罗红霉素对家兔体内格列吡嗪的药动学有明显的影响,临床合用两药时需要注意调整剂量以防发生低血糖危害。

Pharmacokinetic study of glipizide effected by roxithromycin in rabbits

AIM: To study the influence of roxithromycin on the pharmacokinetics of glipizide capsule in healthy and diabetic rabbits METHODS: Glipizide(5 mg) was taken orally once to every rabbit.After 2 weeks of clearing stage,roxithromycin(50.0 mg) was administered daily by intra peritoneal injection bid for 3 d,then glipizide was taken orally at the same dosage on the 4 d.The blood was drawn from ear vein before and 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 with pharmacokinetic software DAS2.0.The pharmacokinetics of glipizide in rabbits administered with or without roxithromycin were analyzed by auto-control.RESULTS: The concentration time-curves were fit to the one-compartment model.In healthy rabbits administered with glipizide,the t1/2, Cmax,AUC values were(2.9±0.4) h,(5815±940) μg/L,(58919±860)μg·h·L-1.In healthy rabbits administered with glipizide and roxithromycin,the t1/2,Cmax,AUC values were(3.5±0.9) h,(6165±764)μg/L,(76515±1830) μg·h·L-1.In diabetes rabbits administered with glipizide,the t1/2,Cmax,AUC values were(1.7±0.4) h,(4307±580) μg/L,(32469±786)μg·h·L-1.In diabetes rabbits administered with glipizide and roxithromycin,the t1/2,Cmax,AUC values were(3.2±1.5)h,(8531±1479) μg/L,(76489±1588) μg·h·L-1.There were notable differences on t1/2,Cmax,AUC values of glipizide in rabbits administered with or without roxithromycin. CONCLUSION: Roxithromycin shows significant inhibition on the pharmacokinetics of glipizide.The two drugs in clinical share requiring attention adjustment dose in order to avoid hypoglycemia hazards.