格列吡嗪和格列本脲对氯沙坦药动学的影响

Effect of Glipizide and Glibenclamide on the Pharmacokinetics of Losartan

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 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 Cmax of losartan and E-3174 were significantly increased and the clearance of losartan was significantly decreased; when co-administrated with glibenclamide, only the Tmax 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.