高原环境对大鼠体内呋塞米和醋甲唑胺血浆蛋白结合率的影响

Effects of hypoxia environment at high altitude on serum protein-binding rate of furosemide and methazolamide in rats

目的:对平原与高原组大鼠体内呋塞米和醋甲唑胺的血浆蛋白结合率差异进行比较。方法:Wistar大鼠于平原地区禁食12 h后分别将呋塞米0.001 7 g、醋甲唑胺0.004 9 g片剂灌胃给药,清洗期后,急进高原灌胃给药。给药后0.66、2、4 h由眼眶后静脉丛取血(呋塞米),醋甲唑胺采血时间点为0.66、2、8 h,采用超滤法测定呋塞米和醋甲唑胺血浆蛋白结合率,LCMS/MS方法测定呋塞米和醋甲唑胺血浓度。结果:急进高原后呋塞米蛋白结合率略有增高,但无显著性差异。而醋甲唑胺组蛋白结合率增高明显,平原组和急进高原组血浆蛋白结合率值分别为(21.52±1.22)%、(73.98±2.09)%。结论:本研究发现急进高原后大鼠体内呋塞米和醋甲唑胺血浆蛋白结合率变化不同,血浆蛋白结合率的变化可能会影响药物药动学特征。

OBJECTIVE To compare serum protein-binding rate of furosemide and methazolamide in rats living at low altitude and those after quickly acute exposure to high altitude.METHODS Rats were administered with 0.001 7 g furosemide tablets and 0.004 9 g methazolamide tablets at low altitude,then quickly exposed to high altitude.Rats residing at low altitude were exposed to high altitude after washout period.Blood samples were collected from veins of eye socket 0.66,2,4 hours after administration of furosemide and 0.66,2,8 hours after administration of methazolamide.Protein binding rate was determined by ultrafiltration method and plasma concentration was determined by LC-MS/MS.RESULTS Protein binding rate of furosemide was unchanged.Protein binding rate of methazolamide was higher at high altitude（21.52±1.22）% compared with rats at low altitude（73.98±2.09）%.CONCLUSION Protein binding rates of furosemide and methazolamide were significantly different and change of protein binding will further affect pharmacokinetics of drugs.