目的 探究瑞舒伐他汀對格列喹酮在2型糖尿病大鼠體內藥動學參數(shù)的影響。方法 采用高糖高脂飼料喂養(yǎng)與ip低劑量鏈脲佐菌素（40 mg/kg）相結合的方法制備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），于給藥后0.5、1.5、2、2.5、4、6、8 h頸動脈取血。采用高效液相色譜法測定大鼠血漿中格列喹酮的濃度，繪制血藥濃度–時間曲線，計算藥動學參數(shù)。結果 在2型糖尿病大鼠中，與格列喹酮單用相比，與瑞舒伐他汀聯(lián)用之后，格列喹酮的t_1/2明顯延長（P＜0.01），血漿清除率（CL）明顯降低（P＜0.01），達峰濃度（C_max）、藥–時曲線下面積（AUC）明顯增加（P＜0.01）。結論 瑞舒伐他汀和格列喹酮聯(lián)用后，可明顯改變格列喹酮在2型糖尿病大鼠體內的藥動學參數(shù)，提高其血藥濃度。因此，當兩藥聯(lián)用時，應特別注意潛在的藥物相互作用和格列喹酮的使用劑量。

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 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.

R286.02

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