氯沙坦与格列美脲在人肝微粒体中的药物相互作用

目的：研究氯沙坦与格列美脲在人肝微粒体中的药物相互作用。方法：200 μL人肝微粒体孵育体系中加入氯沙坦与格列美脲各1~10 μmol·L^-1，于37℃水浴中孵育30 min，终止反应后的样品经处理，应用UPLC-MS/MS法同时检测氯沙坦和格列美脲代谢产物的生成量，采用Dixon作图并计算格列美脲抑制氯沙坦的K_i值以考察格列美脲和氯沙坦的相互抑制作用。结果：在1~10 μmol·L^-1的浓度范围内，格列美脲对氯沙坦表现出明显的抑制作用，相应的K_i值为（0.407 7±0.086 2）μmol·L^-1；氯沙坦仅在格列美脲浓度为1 μmol·L^-1时表现出抑制作用。结论：在人肝微粒体孵育体系中，格列美脲对氯沙坦的抑制作用强于氯沙坦对格列美脲的抑制作用。氯沙坦和格列美脲在人体内的相互作用有待进一步的人体药代动力学研究。

Drug-drug interaction of losartan and glimepiride in human liver microsomes

OBJECTIVE To observe the drug-drug interaction of losartan and glimepiride in human liver microsomes.METHODS Losartan (1-10 μmol·L^-1) and glimepiride (1-10 μmolL^-1) were mixed to a 200 μL incubation system and incubated at 37℃ for 30 min in a shaking water bath. The samples were analyzed using a UPLC-MS/MS method to determine the generation of metabolites of losartan and glimepiride. Dixon plotting and calculation of K_i value were performed to evaluate the inhibitory effect of glimepiride on losartan and losartan on glimepiride.RESULTS Glimepiride showed significant inhibitory effect on losartan at the concentration of 1-10 μmol·L^-1 losartan with a K_i value of 0.407 7±0.086 2 μmol·L^-1. Losartan only showed inhibitory effect on glimepiride at the concentration of 1 μmol·L^-1 glimepiride.CONCLUSION In the incubation system of human liver microsomes, the inhibitory effect of glimepiride on losartan is stronger than that of losartan on glimepiride. The interaction between losartan and glimepiride in human body needs further pharmacokinetic investigation in vivo.