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

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t_1/2明显延长（P＜0.01），血浆清除率（CL）明显降低（P＜0.01），达峰浓度（C_max）、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。

Effects of rosuvastatin on pharmacokinetics parameters of gliquidone in type 2 diabetic rats

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 t_1/2 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 (C_max) 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.