格列吡嗪和格列本脲对氯沙坦药动学的影响

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。

Effect of Glipizide and Glibenclamide on the Pharmacokinetics of Losartan

OBJECTIVE To study the effect of glipizide and glibenclamide on the pharmacokinetics of losartan in rats. METHODS Fifteen rats were randomly divided into 3 groups(control group, glipizide group and glibenclamide group) and administrated orally with 0.5%CMC, 10 mg·kg^-1 glipizide and 10 mg·kg^-1 glibenclamide, respectively. The 5 mg·kg^-1 losartan potassium was administrated orally to the rats 0.5 h later and blood samples were collected via tail vein at different time point, which were further processed and analyzed for the concentration of losartan and E-3174 by HPLC. The pharmacokinetic parameters were calculated by DAS, followed by statistical analysis. RESULTS When co-administrated with glipizide, the AUC, MRT and C_max of losartan and E-3174 were significantly increased and the clearance of losartan was significantly decreased; when co-administrated with glibenclamide, only the T_max of losartan and MRT of E-3174 were altered. CONCLUSION Glipizide significantly affected the pharmacokinetics of losartan and its metabolite E-3174 in rats. In clinic, when these two drugs are co-administrated, drug adverse reaction of losartan induced by drug-drug interaction should be paid attention to.