辛伐他汀 瑞舒伐他汀对大鼠体内格列吡嗪药动学影响

Effects of Simvastatin and Rosuvastatin on Pharmacokinetics of Glipizide in Rats

目的考察辛伐他汀、瑞舒伐他汀在大鼠体内对格列吡嗪药动学的影响。方法雄性SD大鼠18只,随机分为辛伐他汀组、瑞舒伐他汀组和对照组,每组6只。辛伐他汀组灌胃给予辛伐他汀10 mg·kg^(-1);瑞舒伐他汀组灌胃给予瑞舒伐他汀10mg·kg^(-1);对照组灌胃给予同等体积的溶剂;各组大鼠于给药0.5h后灌胃给予格列吡嗪10mg·kg^(-1),规定时间点尾静脉取血,HPLC法测定格列吡嗪浓度,DAS 3.2.1计算药动学参数,考察辛伐他汀与瑞舒伐他汀对格列吡嗪药动学的影响。结果辛伐他汀组与瑞舒伐他汀组的C_(max)、AUC较对照组均减小,有统计学差异(P<0.05,P<0.01);而CLz/F较对照组提高,具有统计学意义(P<0.05,P<0.01)。结论辛伐他汀和瑞舒伐他汀对大鼠体内格列吡嗪的药动学存在影响,可减小格列吡嗪浓度,并且缩短其达峰时间,据此建议临床上两药合用时,应严密监测患者格列吡嗪浓度以及血糖值。

To investigate the effect of simvastatin and rosuvastatin on the pharmacokinetics of glipizide in rats.Methods Eighteen healthy male SD rats, 230-270 g, were randomly and equally divided into the simvastatin group,rosuvastatin group and control group.The two experimental groups were fed with 10 mg ·kg^-1 simvastatin and 10 mg ·kg^-1rosuvastatin respectively, and 0.5 h later, all the groups were fed with 10 mg ·kg^-1 glipizide. Blood was drawn from the caudal vein at the indicated time point after oral administration of glipizide. The concentrations of glipizide were measured by HPLC while the pharmacokinetic parameters were calculated by DAS3.2.1 software. Results Compared with the control group, C max and AUC of the simvastatin group and rosuvastatin group decreased,and the difference was statistically significant.CLz/F in the experiment groups was higher than that in the control group,and the difference was statistically significant.Conclusion Simvastatin and rosuvastatin have sig- nificant effect on the pharmaeokinetics of glipizide, suggesting that the concentration of glipizide and blood sugar levels of patients should be closely monitored.