目的 探討氯沙坦對格列吡嗪在2型糖尿病大鼠體內(nèi)藥動學(xué)參數(shù)的影響。方法 以高糖高脂飼料喂養(yǎng)、ip低劑量鏈脲佐菌素誘導(dǎo)2型糖尿病模型大鼠為研究對象，ig氯沙坦片5 mg/kg，給藥1 h后ig格列吡嗪5 mg/kg，于給藥后1、2、3、4、5、6、8、10、12 h采集血漿樣品，采用HPLC法測定血漿中的格列吡嗪質(zhì)量濃度，繪制其血漿平均藥物濃度-時間曲線；計算格列吡嗪在大鼠體內(nèi)的主要藥動學(xué)參數(shù)。結(jié)果 與健康大鼠比較，格列吡嗪在2型糖尿病大鼠體內(nèi)消除半衰期明顯延長（P<0.05）。在2型糖尿病大鼠中，與單用格列吡嗪比較，格列吡嗪的達(dá)峰濃度（C_max）、時量曲線下面積（AUC）明顯增加（P<0.05），達(dá)峰時間（t_max）明顯減?。?i>P<0.05）。結(jié)論 在糖尿病病理狀態(tài)下，格列吡嗪的藥動學(xué)發(fā)生了一定的改變。聯(lián)合用藥時，氯沙坦可明顯提高格列吡嗪的血藥濃度和生物利用度。

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

安徽省科技攻關(guān)項目（1501041157）