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目的研究格列吡嗪和格列本脲对氯沙坦在大鼠体内药动学的影响。方法将15只大鼠随机分成对照组、格列吡嗪组和格列本脲组,分别灌胃给予0.5%CMC、10 mg·kg~(-1)格列吡嗪和10 mg·kg~(-1)格列本脲,0.5 h后灌胃给予5 mg·kg~(-1)氯沙坦钾,经尾静脉予不同时间点采集血样,采用HPLC测定血样中氯沙坦及其代谢产物E-3174的浓度。采用DAS计算各组主要的药动学参数,并进行统计学分析。结果合用格列吡嗪后,氯沙坦和E-3174的AUC、MRT和峰浓度均明显增加,氯沙坦的清除率减小;合用格列本脲后,氯沙坦的达峰时间提前,E-3174的MRT延长。结论与同剂量的格列本脲相比,格列吡嗪对氯沙坦及其代谢产物在大鼠体内的药动学影响较大。临床上合用氯沙坦和格列吡嗪时,应注意潜在的药物相互作用所致的药物不良反应。
Objective To study the effects of glipizide and glibenclamide on the pharmacokinetics of losartan in rats. Methods Fifteen rats were randomly divided into control group, glipizide group and glibenclamide group. Rats were given 0.5% CMC, 10 mg · kg -1 glipizide and 10 mg · kg ~ (-1) glibenclamide. After 0.5 h, losartan 5 mg · kg -1 was given intragastrically, blood samples were taken from the tail vein at different time points, and losartan and its metabolites Concentration of product E-3174. The main pharmacokinetic parameters of each group were calculated by DAS, and statistical analysis was made. Results After treated with glipizide, the AUC, MRT and peak concentrations of losartan and E-3174 were significantly increased and the clearance rate of losartan was decreased. Losartan peaked with paclitaxel , MRT extension of E-3174. Conclusion Compared with the same dose of glibenclamide, glipizide on losartan and its metabolites in rats pharmacokinetics greater impact. Clinically, losartan and glipizide should pay attention to adverse drug reactions caused by potential drug interactions.