目的 探讨氯沙坦对格列吡嗪在2型糖尿病大鼠体内药动学参数的影响。方法 以高糖高脂饲料喂养、ip低剂量链脲佐菌素诱导2型糖尿病模型大鼠为研究对象，ig氯沙坦片5 mg/kg，给药1 h后ig格列吡嗪5 mg/kg，于给药后1、2、3、4、5、6、8、10、12 h采集血浆样品，采用HPLC法测定血浆中的格列吡嗪质量浓度，绘制其血浆平均药物浓度-时间曲线；计算格列吡嗪在大鼠体内的主要药动学参数。结果 与健康大鼠比较，格列吡嗪在2型糖尿病大鼠体内消除半衰期明显延长（P<0.05）。在2型糖尿病大鼠中，与单用格列吡嗪比较，格列吡嗪的达峰浓度（C_max）、时量曲线下面积（AUC）明显增加（P<0.05），达峰时间（t_max）明显减小（P<0.05）。结论 在糖尿病病理状态下，格列吡嗪的药动学发生了一定的改变。联合用药时，氯沙坦可明显提高格列吡嗪的血药浓度和生物利用度。

Objective To investigate the effect of losartan on pharmacokinetic parameters of glipizide in type 2 diabetes rats in vivo. Methods Type 2 diabetes model rats were induced by high sugar and fat feed and ip low-dose streptozotocin. Rats were ig administered with Losartan Tablets 5 mg/kg, then were ig administered with Losartan Tablets 5 mg/kg after 1 h. Plasma samples were taken at 1, 2, 3, 4, 5, 6, 8, 10, and 12 h after administration. The concentrations of glipizide in plasma samples were determined by HPLC, and the average concentration time curve of glipizide in plasma was drawn. The main pharmacokinetic parameters of glipizide in rats were calculated. Results Compared with healthy rats, the elimination half-life of glipizide in type 2 diabetes rats was significantly prolonged (P < 0.05). In type 2 diabetes rats, the peak concentration (C_max) and the area under the curve (AUC) of glipizide were significantly increased (P < 0.05), and peak time (t_max) was significantly reduced compared with glipizide alone (P < 0.05). Conclusion The pharmacokinetics of glipizide has changed in the pathological state of diabetes. When they are combined, losartan can significantly increase the plasma concentration and bioavailability of glipizide.

R969.1

安徽省科技攻关项目（1501041157）