摘要
目的探究瑞舒伐他汀对格列喹酮在2型糖尿病大鼠体内药动学参数的影响。方法采用高糖高脂饲料喂养与ip低剂量链脲佐菌素(40 mg/kg)相结合的方法制备SD大鼠2型糖尿病模型。2型糖尿病大鼠先ig瑞舒伐他汀(10 mg/kg),0.5 h后再ig格列喹酮(15 mg/kg),于给药后0.5、1.5、2、2.5、4、6、8 h颈动脉取血。采用高效液相色谱法测定大鼠血浆中格列喹酮的浓度,绘制血药浓度–时间曲线,计算药动学参数。结果在2型糖尿病大鼠中,与格列喹酮单用相比,与瑞舒伐他汀联用之后,格列喹酮的t1/2明显延长(P<0.01),血浆清除率(CL)明显降低(P<0.01),达峰浓度(Cmax)、药–时曲线下面积(AUC)明显增加(P<0.01)。结论瑞舒伐他汀和格列喹酮联用后,可明显改变格列喹酮在2型糖尿病大鼠体内的药动学参数,提高其血药浓度。因此,当两药联用时,应特别注意潜在的药物相互作用和格列喹酮的使用剂量。
Objective To investigate the effects of rosuvastatin on the pharmacokinetics parameters of gliquidone in type 2 diabetic rats.Methods Type 2 diabetic models were made in SD rats by feeding high-sugar/high-fat food and ip administered with streptozotocin(40 mg/kg).Type 2 diabetic rats were ig administered with rosuvastatin(10 mg/kg),and then gliquidone(15 mg/kg)0.5 h later.The carotid blood samples were taken at 0.5,1.5,2,2.5,4,6,and 8 h after administration,respectively.The concentration of gliquidone in plasma was determined by HPLC method.The concentration-time curve and main pharmacokinetic parameters of gliquidone in plasma were calculated.Results In type 2 diabetic rats,compared with gliquidone alone,the t1/2 of gliquidone combined with rosuvastatin was significantly prolonged(P<0.05),the plasma clearance(CL)was significantly decreased(P<0.01),and the peak concentration(Cmax)and the area under the curve(AUC)were significantly increased(P<0.01).Conclusion Rosuvastatin combined with gliquidone can significantly change the pharmacokinetic parameters of gliquidone in type 2 diabetic rats and increase its plasma concentration.Therefore,when the two drugs are used together,special attention should be paid to the potential drug interaction and the dosage of gliquidone.
作者
夏荣平
朱恩泽
张华斌
洪宗元
XIA Rong-ping;ZHU En-ze;ZHANG Hua-bin;HONG Zong-yuan(Department of Pharmacology,Wannan Medical College,Wuhu 241003,China)
出处
《现代药物与临床》
CAS
2022年第5期970-975,共6页
Drugs & Clinic
基金
安徽省科技攻关计划项目(1501041157)。
